WO2022139812A1 - Dual mechanical heating control - Google Patents
Dual mechanical heating control Download PDFInfo
- Publication number
- WO2022139812A1 WO2022139812A1 PCT/US2020/066601 US2020066601W WO2022139812A1 WO 2022139812 A1 WO2022139812 A1 WO 2022139812A1 US 2020066601 W US2020066601 W US 2020066601W WO 2022139812 A1 WO2022139812 A1 WO 2022139812A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- sample preparation
- heaters
- cartridge module
- preparation cartridge
- sample
- Prior art date
Links
- 238000010438 heat treatment Methods 0.000 title claims description 77
- 230000009977 dual effect Effects 0.000 title description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 220
- 239000000463 material Substances 0.000 claims description 88
- 238000000034 method Methods 0.000 claims description 37
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 230000004044 response Effects 0.000 claims description 10
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- 229920000089 Cyclic olefin copolymer Polymers 0.000 claims description 6
- 239000004713 Cyclic olefin copolymer Substances 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 5
- 239000002184 metal Substances 0.000 claims description 5
- 229920000049 Carbon (fiber) Polymers 0.000 claims description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 4
- 229910052782 aluminium Inorganic materials 0.000 claims description 4
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 239000004917 carbon fiber Substances 0.000 claims description 4
- 229910052802 copper Inorganic materials 0.000 claims description 4
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- 229910044991 metal oxide Inorganic materials 0.000 claims description 4
- 150000004706 metal oxides Chemical class 0.000 claims description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 4
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 claims description 4
- 239000000523 sample Substances 0.000 description 322
- 239000012472 biological sample Substances 0.000 description 24
- 238000002156 mixing Methods 0.000 description 20
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- 102000039446 nucleic acids Human genes 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
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- 230000000295 complement effect Effects 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
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- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
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Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/44—Sample treatment involving radiation, e.g. heat
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L7/00—Heating or cooling apparatus; Heat insulating devices
- B01L7/04—Heat insulating devices, e.g. jackets for flasks
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L7/00—Heating or cooling apparatus; Heat insulating devices
- B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/14—Process control and prevention of errors
- B01L2200/143—Quality control, feedback systems
- B01L2200/147—Employing temperature sensors
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/18—Means for temperature control
- B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5082—Test tubes per se
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00346—Heating or cooling arrangements
- G01N2035/00425—Heating or cooling means associated with pipettes or the like, e.g. for supplying sample/reagent at given temperature
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00465—Separating and mixing arrangements
Definitions
- Sample heating in devices that effect biological or chemical processes in sample preparation cartridge modules can be crucial, for example in sample preparation devices.
- Figure 1 A and Figure 1 B are block diagrams of an example device with dual mechanical heating control, with heaters thereof in rest positions and sample engaging positions respectively.
- Figure 2A is a perspective view of an example sample preparation device that incorporates the device of Figure 1 .
- Figure 2B is a block diagram of the device of Figure 2A.
- Figure 3 is a block diagram of the device of Figure 2A showing a cassette and sample preparation cartridge module in a heating position.
- Figure 4A, Figure 4B, Figure 4C, and Figure 4D show heaters of the device of Figure 2A in rest positions and sample engaging positions respectively, as well as a sample preparation cartridge module at the sample engaging positions.
- Figure 5 is a block diagram showing control components of the device of Figure 2A, such as a processor, to implement dual mechanical heating control.
- Figure 6 is a flow diagram of an example method for dual mechanical heating control.
- Figure 7 depicts a cross-section of an example sample preparation cartridge module.
- a biological component can be intermixed with other components in a biological sample that can interfere with subsequent analysis.
- biological component can refer to materials of various types, including proteins, cells, cell nuclei, nucleic acids, bacteria, viruses, or the like, that can be present in a biological sample.
- a “biological sample” can refer to a fluid or a dried or lyophilized material obtained for analysis from a living or deceased organism. Isolating the biological component from other components of the biological sample can permit subsequent analysis without interference and can increase an accuracy of the subsequent analysis.
- Isolation can also be referred to as “purification”, whereby biological component may be separated from the rest of the biological sample after introduction to a sample preparation cartridge module interchangeably referred to hereafter as a sample container, a sample dispensing container, a cartridge module, and the like. It will be understood that the isolated biological component may be output in association with (e.g., bound to) particulate substrate and a reagent solution, or the like.
- isolation or purification refers to the separation of the biological component from other components of the biological sample with which it was originally introduced in the cartridge module, but it does not mean that the biological component is completely isolated when it is dispensed.
- isolation refers to the fact that the biological component is sufficiently separated or “purified” from other components of the original biological sample to facilitate further processing such as detection and/or amplification.
- isolation techniques can include repeatedly dispersing and reaggregating samples.
- the repeated dispersing and re-aggregating can result in a loss of a quantity of the biological component.
- isolating a biological component with some of these techniques can be complex, time consuming, and labor intensive and can result in less than maximum yields of the isolated biological component.
- Such Isolation techniques are done using specific devices.
- Obtaining precise biological sample preparation devices can be challenging due to many moving parts present in the devices, for example to move a carriage holding a cartridge of sample dispensing containers relative to sample receiving wells.
- the cartridge may hold a plurality of the sample dispensing containers or sample preparation devices or sample preparation cartridge modules which contain different respective biological samples.
- sample dispensing containers or sample preparation devices or sample preparation cartridge modules may heat the samples to perform for example, lysis on cells in the biological samples to release biological component of interest, coming from the biological sample, may be a nucleic acid (such as DNA or RNA).
- Resulting sample fluid may be drawn through a fluid density gradient in the sample dispensing containers and dispensed into sample receiving wells, which may be transferred to further analytical assay such as, for example, a Polymerase Chain Reaction (PCR).
- PCR Polymerase Chain Reaction
- initial quantities of the biological component of interest present in the biological sample may be small, precise dispensing of the component of interest from the sample dispensing containers into the sample receiving wells should occur so as to not lose any content and/or to prevent cross-contamination between samples.
- a precise determination of a position of a shuttle and/or well carriage, that holds the sample receiving wells, relative to the carriage is important, and vice versa.
- the device of the present disclosure is a device that can be used to prepare sample to be used in a process of preparing samples for a PCR (polymerase chain reaction) assay.
- PCR assays are processes that can rapidly copy millions to billions of copies of a very small DNA or RNA sample.
- PCR can be used for many different application, included sequencing genes, diagnosing viruses, identifying cancers, and others.
- sequencing genes included in the PCR process, a small sample of DNA or RNA is combined with reactants that can form copies of the DNA or RNA.
- the biological sample comprises a biological component.
- the biological component of interest coming from the biological sample, may be a nucleic acid (such as DNA or RNA).
- a particulate substrate can be configured to be associated with the biological component, to isolate the biological component from the biological sample.
- the particulate substrate comprises paramagnetic beads and/or any magnetizing particle and/or magnetizing microparticles.
- the biological component comprises nucleic acids such as DNA and/or RNA that may be extracted from the biological sample by lysing, bound to magnetic particulate substrate, and separated from the lysate and dragged towards an output by an externally generated (para)magnetic force.
- Lysate may refer to the fluid containing the material resulting from the lysis of a biological sample. Such lysis may release the biological component that is contained therein. Lysing itself may include mixing and/or heating the biological sample, chemically lysing the biological sample, and/or a combination of the foregoing.
- sample heating in such devices that process biological samples, as described above, in sample containers and/or sample preparation cartridge modules, can be crucial.
- a device that includes two heaters attached to respective mechanical devices that move the heaters between respective sample engaging positions, to heat a sample preparation cartridge module at the sample engaging positions, and respective rest positions and/or a cooling positions, at which the heaters do not heat the sample preparation cartridge module.
- the two heaters are generally positioned and shaped to engage a sample preparation cartridge module from opposite directions.
- the device includes two temperature sensors to respectively measure temperature of the two heaters.
- the device further includes an actuator to mix a sample in the sample preparation cartridge module at different speeds.
- a circuit generally controls the actuator to mix a sample in the sample preparation cartridge module at the different speeds while concurrently controlling one or both of the two mechanical devices to move one or both of the two heaters to the respective sample engaging positions or the respective rest positions depending on temperatures measured by the two temperature sensors or a speed of the actuator.
- the device may be incorporated into the aforementioned sample preparation device, and the like, which receives sample preparation cartridge module containing biological samples, for example human cells to be tested for presence of a biological component of interest; hence, with two heaters that may singly, or doubly, engage a sample preparation cartridge module, the sample preparation device may achieve flexibility in performing heating on a sample in the sample preparation cartridge module for lysis, and the like.
- the circuit may control one or both of two heaters to engage the sample preparation cartridge module from opposite directions depending on a temperature of the two heaters, as measured by a temperature sensor, and/or depending on a speed of the actuator, for example to better control lysis in the samples.
- a sample preparation cartridge module may be formed from a first material that has a first thermal conductivity. Internal walls of the sample preparation cartridge module are understood to be formed from the first material, which may be chemically inert to samples, and other materials, that are contained within the sample preparation cartridge module by the internal wall.
- a heating region of the sample preparation cartridge module for example within which a sample resides for lysis to be performed thereon, may have an external wall that includes a second material having a second thermal conductivity higher than the first thermal conductivity. The second material may be otherwise absent from internal walls of the sample preparation cartridge module as well regions of the sample preparation cartridge module other than the heating region.
- the second material may hence promote thermal conductivity in the heating region to better heat a sample contained therein to perform lysis; absence of the second material at the internal walls may allow the second material to include materials reactive to samples and/or other chemicals contained within the sample preparation cartridge module. Furthermore, absence of the second material outside the heating region may better contain heat in the heating region and/or prevent heat from being conducted to other regions of the sample preparation cartridge module, as the other regions are formed from the first material that has the first thermal conductivity lower than the second thermal conductivity of the second material.
- a first aspect of the specification provides a device comprising: two heaters shaped to engage a sample preparation cartridge module from opposite directions; two mechanical devices to respectively move the heaters between respective sample engaging positions and respective rest positions; two temperature sensors to respectively measure temperature of the two heaters; an actuator to mix a sample in the sample preparation cartridge module at different speeds; and a circuit communicatively coupled to the two heaters, the two mechanical devices, and the actuator, to circuit to: control the actuator to mix a sample in the sample preparation cartridge module at the different speeds; and control one or both of the two mechanical devices to move one or both of the two heaters to the respective sample engaging positions or the respective rest positions depending on temperatures measured by the two temperature sensors or a speed of the actuator.
- the circuit may be further to, in response to the temperatures meeting a temperature condition, control one or both of the heaters to stop heating.
- the two heaters may be further shaped to engage a heating region of the sample preparation cartridge module having an internal wall formed from a first material having a first thermal conductivity, and an external wall that includes a second material having a second thermal conductivity higher than the first thermal conductivity, the second material absent from the internal wall, wherein adjacent regions of the sample preparation cartridge module are absent the second material to contain heat from the heaters at the heating region.
- the two mechanical devices may comprise respective robotic arms, the two heaters located at respective end effectors of the robotic arms.
- the circuit may be further to independently control respective power to the two heaters.
- a second aspect of the specification provides a method comprising: controlling, at a sample preparation device into which a sample preparation cartridge module has been loaded, an actuator to mix a sample in the sample preparation cartridge module at different speeds; and controlling, at the sample preparation device, one or both of two movable heaters to engage the sample preparation cartridge module from opposite directions depending on a temperature of the two movable heaters, as measured by a temperature sensor, or a speed of the actuator.
- the method of the second aspect may further comprise: controlling the actuator to a first speed; controlling both of the two movable heaters to engage the sample preparation cartridge module while the actuator is at the first speed; and in response to the temperature of the two movable heaters reaching a given temperature: controlling the actuator to a second speed; and controlling both of the two movable heaters to disengage the sample preparation cartridge module while the actuator is at the second speed.
- the method of the second aspect may further comprise: controlling the actuator to a first speed; controlling one of the two movable heaters to engage the sample preparation cartridge module while the actuator is at the first speed; and in response to the temperature reaching a given temperature: controlling the actuator to a second speed; and controlling the one of the two movable heaters that has engaged the sample preparation cartridge module to disengage the sample preparation cartridge module while the actuator is at the second speed.
- the method of the second aspect may further comprise: controlling both of the two movable heaters to engage the sample preparation cartridge module while the actuator is at a first speed; controlling both of the two movable heaters to disengage the sample preparation cartridge module while the actuator is at a second speed; and controlling one of the two movable heaters to engage the sample preparation cartridge module while the actuator is at a third speed.
- the method of the second aspect may further comprise: controlling both of the two movable heaters to engage the sample preparation cartridge module until the temperature reaches a first given temperature; controlling both of the two movable heaters to disengage the sample preparation cartridge module until the temperature reaches a second given temperature; and controlling one of the two movable heaters to engage the sample preparation cartridge module until the temperature reaches a third given temperature.
- a third aspect of the present specification provides a sample preparation cartridge module comprising: a first region comprising: an internal wall formed from a first material having a first thermal conductivity, and an external wall that includes a second material having a second thermal conductivity higher than the first thermal conductivity, the second material absent from the internal wall; and a second region comprising: a respective internal wall and a respective external wall both formed from the first material, the second material absent from the second region, the first region and the second region being fluidly connected, the first region comprising a heating region and the second region storing a heat sensitive chemical.
- the external wall of the first region may comprise an insert of the second material, or a mixture of the first material and the second material.
- the first material may comprise a cyclic olefin copolymer (CoC) material.
- CoC cyclic olefin copolymer
- the second material may comprise metal, aluminum, copper, carbon, carbon fiber, carbon powder, graphite, a metallic powder, a metal oxide powder, or aluminum oxide.
- the external wall of the first region may be shaped to mate with a heater.
- Figure 1 A and Figure 1 B show respective block diagrams of an example device 100 with dual mechanical heating control with heaters thereof in respective rest positions and sample positions. While described in more detail below, it is understood that components of the device 100 may be components of a larger device used for medical testing of samples including, but not limited to, sample preparation. In particular, the device 100 may be used in a larger sample preparation device to process samples in sample preparation cartridge modules, and the like. Such a sample preparation device is described below with respect to Figure 2A and Figure 2B.
- the device 100 generally comprises two heaters 102-1 , 102-2, represented in Figure 1A and Figure 1 B as resistors, and two temperature sensors 104-1 , 104-2 represented in Figure 1A and Figure 1 B as thermistors.
- the heaters 102-1 , 102-2 are interchangeably referred to hereafter, collectively, as the heaters 102 and, generically, as a heater 102. This convention will be used throughout the present specification; for example, the temperature sensors 104-1 , 104-2 may be referred as the sensors 104 and/or as a sensor 104.
- the device 100 further comprises two mechanical devices 106-1 , 106-2 (e.g. mechanical devices 106 and/or a mechanical device 106) to move respective heaters 102 between respective sample engaging positions 108, as depicted in Figure 1 B, and respective rest positions 110, as depicted in Figure 1A.
- two mechanical devices 106-1 , 106-2 e.g. mechanical devices 106 and/or a mechanical device 106 to move respective heaters 102 between respective sample engaging positions 108, as depicted in Figure 1 B, and respective rest positions 110, as depicted in Figure 1A.
- the heaters 102 (and/or the mechanical devices 106) are shaped, and positioned relative to one another, to engage a sample preparation cartridge module from opposite directions.
- the heaters 102 and/or the mechanical devices 106 may include respective chassis, and the like, that are shaped complementary to a sample preparation cartridge module located at the sample engaging positions 108 (e.g. see Figure 4B).
- chassis of the heaters 102 and/or the mechanical devices 106 are concave to engage a cylindrically shaped sample preparation cartridge module at the sample engaging positions 108.
- the heaters 102 and/or the mechanical devices 106 may be any suitable shape to heat a sample preparation cartridge module (e.g. which may also be of any suitable shape).
- the device 100 further comprises a circuit 114 and an actuator 116.
- the actuator 116 is generally to mix a sample in a sample preparation cartridge module between the two heaters 102 at different speeds and may be actuated by a mixer actuator, not depicted (however see Figure 2B). Such mixing is indicated by an arrow 118 in Figure 1 B showing the actuator 116 being rotated back and forth (and the like). Interaction of the actuator 116 with a sample preparation cartridge module is described in more detail below.
- the circuit 114 is communicatively coupled to the heaters 102, the temperature sensors 104, the mechanical devices 106 and the actuator 116. While electrical connections from the circuit 114 to the various other components are not explicitly depicted, such electrical connections and/or communicative couplings are represented by double ended arrows between the circuit 114 the mechanical devices 106 and the actuator 116 which may represent wiring, and the like, of the circuit 114 to the various other components.
- the circuit 114 is generally to control the actuator 116 to mix a sample (e.g. a liquid sample) in a sample preparation cartridge module, engaged by the heaters 102, at the different speeds; and control one or both of the two mechanical devices 106 to move one or both of the two heaters 102 to the respective sample engaging positions 108 or the respective rest positions 110, depending on temperatures measured by the two temperature sensors 104 or a speed of the actuator 116.
- a sample e.g. a liquid sample
- the circuit 114 generally controls the mechanical devices 106 to move one or both of the heaters 102 to engage a sample preparation cartridge module while also controlling the speed of the actuator 116; the speed of the actuator 116 may be a given speed at which a sample in the sample preparation cartridge module is to be heated to a particular given temperature, during a given heating/mixing cycle, which may be achieved by controlling the mechanical devices 106 to move one or both of the heaters 102 to engage the sample preparation cartridge module.
- the device 100 further comprises a power source, which powers the components of the device 100, including, but not limited to, the heaters 102, such that the heaters 102 are powered to perform heating.
- a power source may include, but is not limited to, a connection to a mains power supply and/or batteries, and the like,
- the heaters 102 may comprise any suitable heating devices including, but not limited to, the depicted resistors incorporated into chassis, and the like, which may be shaped to engage a sample preparation cartridge module. It is generally understood that the heaters 102 are positioned at the device 100 to be adjacent and/or against (e.g. via a wall of chassis of the heaters 102 and/or the mechanical devices 106) a sample preparation cartridge module at the sample engaging positions 108. It is understood that the chassis of the heaters 102 and/or the mechanical devices 106 may comprise thermally conducting material, such as any suitable combination of metal and/or a thermally conducting plastic, and the like, to conduct heat from the heaters 102 to a sample preparation cartridge module.
- a portion of the material of the chassis of the heaters 102 and/or the mechanical devices 106 that reside against a sample preparation cartridge module may be (e.g. optionally) at least partially elastic, and the like, to at least partially mold around a sample preparation cartridge module at the sample engaging positions 108, to assist with thermal conduction from the heaters 102 to the sample preparation cartridge module.
- the heaters 102 may be controlled to respective on-states or off-states (e.g. on or off) by the circuit 114.
- the heaters 102 may alternatively be controlled to different heating levels in the on-states, to heat a sample preparation cartridge module at the sample engaging positions 108 to different temperatures, as monitored by the temperature sensors 104.
- the heaters 102 may be controlled between an on-state and off- state to heat a sample preparation cartridge module at the sample engaging positions 108 to a given temperature and/or different temperatures using pulse width modulation (PWM) control of the heaters 102 (e.g. to control, by the circuit 114, respective relative time periods that the heaters 102 are respectively on or off).
- PWM pulse width modulation
- the heaters 102 may also heat a sample preparation cartridge module at the sample engaging positions 108 to different temperatures by the circuit 114 controlling the mechanical devices 106 to move the heaters 102 to different positions, relative to the sample engaging positions 108. For example, the closer the heaters 102 are to the sample engaging positions 108, the more heating of a sample preparation cartridge module at the sample engaging positions 108 may occur.
- control of the mechanical devices 106 may also occur according to PWM control (e.g. to control, by the circuit 114, respective relative time periods that the heaters 102 are at respective sample engaging positions 108 or the respective rest positions 110).
- the heaters 102 are independently movable relative to the sample engaging positions 108 and hence may alternatively be referred to as movable heaters 102.
- the heaters 102 may be controlled to a given temperature (e.g. by the circuit 114) in a feedback loop, based on feedback from the sensors 104.
- the temperatures sensors 104 may comprise any suitable temperature sensing device and/or circuit including, but not limited to, the depicted thermistors incorporated into respective chassis, and the like, at which the respective heaters 102 are also incorporated. It is generally understood that the sensors 104 is positioned at the device 100 to be adjacent and/or against (e.g. via a wall of a chassis of the heaters 102 and/or the mechanical devices 106) a sample preparation cartridge module at the sample engaging positions 108. As such, the sensors 104 generally measure temperature changes due to the heaters 102 being turned on or off by the circuit 114 (and/or otherwise being generally controlled by the circuit 114).
- the temperature sensors 104 are depicted as being at a respective chassis, and the like, at which a respective heater 102 is also incorporated, and hence, as depicted, the temperature sensors 104 also move with the heaters 102. Put another way, the temperature sensors 104 may be located at respective heaters 102.
- the temperature sensors 104 may be at respective fixed positions, for example at respective sample engaging positions 108, and include components for engaging a sample preparation cartridge module at the sample engaging positions 108.
- the temperature sensors 104 may be incorporated into respective spring loaded arms which causes the sensors 104 to reside against a sample preparation cartridge module at the sample engaging positions 108.
- a mechanical device 106 may comprise any suitable mechanical device which moves a respective heater 102 between a respective sample engaging position 108 and a respective rest position 110, including, but not limited to, a robotic arm, an arm attached to a servomotor, and the like.
- An optical encoder, and the like, at the robotic arm and/or the servomotor may be used to control a respective mechanical device 106 between a respective sample engaging position 108 and a respective rest position 110.
- the heaters 102 may be understood to be located at respective end effector positions of respective mechanical devices 106 (e.g. ends of the mechanical devices 106 that interact with an environment around the mechanical devices 106 including, but not limited to, a sample preparation cartridge module at the sample engaging positions 108).
- the two mechanical devices 106 may comprise respective robotic arms or respective arms and servomotors, and the two heaters 102 may be located at respective end effector positions of the mechanical devices 106.
- the mechanical devices 106 are depicted as controlling the heaters 102 to the sample engaging positions 108 and the rest positions 110, it is understood that the mechanical devices 106 may alternatively to be controlled (e.g. by the circuit 114) to move the heaters 102 to any suitable respective position between the respective sample engaging positions 108 and the respective rest positions 110, for example to control respective positions of the heaters 102 relative to a sample preparation cartridge module at the sample engaging positions 108 to control a heating cycle at the sample preparation cartridge module.
- Such a heating cycle may include, but is not limited to, respective times that the sample preparation cartridge module are at respective given temperatures as measured by the sensors 104, ramp times to reach such temperatures, cooling times, and the like.
- such a heating cycle may be part of a heating/mixing cycle in which the heaters 102 are controlled to heat while the actuator 116 is controlled to mix.
- the mechanical devices 106 may be controlled (e.g. by the circuit 114) to adjust the position of the heaters 102 by adjusting respective mechanical pressure or respective mechanical force at the sample engaging positions 108.
- respective robotic arms and/or a respective servomotors, and the like, of the mechanical devices 106 may be controlled (e.g. by the circuit 114) to position respective heaters 102 against a sample preparation cartridge module at respective sample engaging positions 108. and apply respective mechanical pressure and/or respective mechanical force to the sample preparation cartridge module at the respective sample engaging positions 108, for example to change and/or control thermal contact and/or thermal conduction between the heaters 102 and a sample preparation cartridge module.
- the mechanical devices 106 may be spring loaded to apply respective mechanical pressure or respective mechanical force at the sample engaging positions 108.
- the circuit 114 may be further to control the mechanical devices 106 to adjust the respective positions of the heaters 102, to control a heating cycle, by adjusting mechanical pressure or mechanical force at the sample engaging positions 108.
- the device 100 and/or the mechanical devices 106 may include respective pressure sensors and/or force sensors to measure pressure and/or force applied by the mechanical devices 106, and such pressure sensors and/or force sensors may be used to control respective pressure and/or force applied by the mechanical devices 106 in a feedback loop and/or feedback loops with the circuit 114.
- the respective pressure and/or force applied by the mechanical devices 106 may be controlled via optical encoder positions of servomotors of the mechanical devices 106 and/or in any other suitable manner.
- a heating cycle, and/or a heating/mixing cycle may also be controlled by controlling respective time periods that the heaters 102 are at the sample engaging positions 108.
- the circuit 114 may be further to control the mechanical devices 106 to adjust the position of the heaters 102, to control a heating cycle, by controlling respective time periods that the heaters 102 are at the sample engaging positions 108.
- the circuit 114 may be further to control a heating cycle by controlling power to the heaters 102, such that a heater 102 or heaters 102 are turned on for a given time period, to a power level or different power levels, and then turned off. Put another way, the circuit 114 may be further to independently control respective power to the two heaters 102.
- the circuit 114 may comprise any suitable combination of components to control the heaters 102, and the mechanical devices 106 based on temperature measured by the sensors 104 or a speed of the actuator 116.
- the circuit 114 may comprise connections to the heaters 102, a power source to power the heaters 102, switches and/or other components to turn the heaters 102 on or off and/or to adjust a current and/or power to the heaters 102 to control the heaters 102 to different heating levels.
- the circuit 114 is to control the heaters 102 to a given temperature and/or given temperatures, for example to control a heating cycle of a sample preparation cartridge module at the sample engaging positions 108.
- the circuit 114 may comprise a proportional-integral- derivative controller (PID) controller and/or PID controllers to control the heaters 102 to a given temperature and/or given temperatures, for example to control a heating cycle and/or heating cycles and/or heating/mixing cycles of a sample preparation cartridge module at the sample engaging positions 108 based on feedback from the sensors 104.
- PID proportional-integral- derivative controller
- the circuit 114 may further comprise connections to the mechanical devices 106, and/or a servomotor thereof, to control the mechanical devices 106 to move the heaters 102 relative to the sample engaging positions 108.
- the circuit 114 may independently control the mechanical devices 106 to move the heaters 102 to respective sample engaging positions 108 or respective rest positions 110.
- the circuit 114 may control one or both of the mechanical devices 106 to move one or both of the heaters 102 to the sample engaging positions 108 to heat a sample preparation cartridge module, and the circuit 114 may control one or both of the mechanical devices 106 to move one or both of heaters 102 to the rest positions 110 to cool the sample preparation cartridge module
- the circuit 114 may control the heaters 102 to be on when the mechanical devices 106 are controlled to move the heaters 102 to the sample engaging positions 108 for example to heat the sample preparation cartridge module to a given temperature and/or for a given period of time to effect lysis and the like at the sample preparation cartridge module. The circuit 114 may then control the heaters 102 to be off when the mechanical devices 106 are controlled to move the heaters 102 to the rest position 110 for example after the given period of time.
- circuit 114 may coordinate mixing speeds of the actuator 116 with given temperatures to which the heaters 102 are heated, as described in more detail below with respect to Figure 6.
- the circuit 114 may be further to, in response to temperatures measured by the sensors 104 meeting a temperature condition, control one or both of the heaters 102 to stop heating and/or control the mechanical devices 106 to move the heaters 102 to the rest positions 110.
- temperature conditions may alternatively be referred to as interlock conditions as, in response to the temperatures meeting a temperature condition, such as a threshold temperature and/or an overshoot temperature, the controlling of the mechanical devices 106 to move the heaters 102 from the sample engaging positions 108 to the rest positions 110 and/or turning off the heaters 102, may act as an interlock to prevent damage to a sample preparation cartridge module at the sample engaging positions 108 and/or sample contained in the sample preparation cartridge module.
- the temperature condition may be that the temperatures monitored by the temperature sensors 104 have reached or exceeded a threshold temperature above which it is undesirable to heat a sample, as at some temperature, above the threshold temperature, biological components of interest in the sample may be damaged and/or the device 100 may be damaged and/or other components of a larger sample preparation device into which the device 100 is incorporated may be damaged.
- a threshold temperature may be referred to as an overheat temperature.
- the temperature condition may be associated with preventing device damage.
- the temperature condition may be that the temperatures monitored by the temperature sensors 104 has reached or exceeded a threshold temperature above which the device 100 may be damaged and/or other components of a larger sample preparation device into which the device 100 is incorporated may be damaged.
- Such rises in temperature, to the threshold temperature may be due to a fault in the heaters 102 and/or the circuit 114 and/or the sample preparation cartridge module any other suitable condition.
- the circuit 114 may include any suitable combination of switches, electrical circuits, and the like which implement functionality as described herein.
- the circuit 114 may further include a general-purpose processor and/or controller or special purpose logic, such as a microprocessor and/or microcontroller (e.g. a central processing unit (CPU) and/or a graphics processing unit (GPU) an integrated circuit or other circuitry), an application specific integrated circuit (ASIC), a Field Programmable Gate Array (FPGA), a programmable array logic (PAL), a programmable logic array (PLA), a programmable logic device (PLD), and the like.
- a microprocessor and/or microcontroller e.g. a central processing unit (CPU) and/or a graphics processing unit (GPU) an integrated circuit or other circuitry
- ASIC application specific integrated circuit
- FPGA Field Programmable Gate Array
- PAL programmable array logic
- PLA programmable logic array
- PLD programmable logic device
- the circuit 114 may be implemented as a hardware element with no software elements (e.g. such as an ASIC, an FPGA, a PAL, a PLA, a PLD etc.).
- a memory of the device 100 e.g. see Figure 5
- instructions for controlling the circuit 114 and/or a processor thereof e.g.
- Such a memory may include, but is not limited to, any suitable combination of a volatile computer-readable medium (e.g., volatile RAM, a processor cache, a processor register, etc.), a non-volatile computer-readable medium (e.g., a magnetic storage device, an optical storage device (e.g. a Digital Versatile Disc (DVD), a paper storage device, flash memory, read-only memory, non-volatile RAM, etc.), and/or the like.
- a volatile computer-readable medium e.g., volatile RAM, a processor cache, a processor register, etc.
- a non-volatile computer-readable medium e.g., a magnetic storage device, an optical storage device (e.g. a Digital Versatile Disc (DVD), a paper storage device, flash memory, read-only memory, non-volatile RAM, etc.
- DVD Digital Versatile Disc
- Figure 2A and Figure 2B respectively depict a perspective view and a block diagram of an example sample preparation device 200 that incorporates aspects of the device 100 of Figure 1 .
- the sample preparation device 200 (interchangeably referred to hereafter as the device 200) includes a chassis 202 that includes a cassette access door 204 for loading a cassette 206 that includes a sample preparation cartridge module 208 and/or sample preparation cartridge modules 208 therein, the sample preparation cartridge module 208 holding a sample for testing as described hereafter. While the sample preparation cartridge modules 208 are depicted herein as being in an elongate shape, the sample preparation cartridge modules 208 may be any suitable shape.
- the chassis 202 further includes a well access door 210 for loading a well holder 212 containing a well 214 and/or wells for receiving processed samples dispensed from the sample preparation cartridge module 208 after processing by the device 200. While only one sample preparation cartridge module 208 is depicted, and eight wells 214, it is understood that the cassette 206 may hold a same number of sample preparation cartridge modules 108 as there are wells 214 at the well holder 212. For example, as depicted, there may be eight sample preparation cartridge modules 208 and eight wells 214.
- the components of the device 200 may cause the cassette 206 and the well holder 212 to be loaded into the device 200 in any suitable relative orientation including, but not limited to, about parallel to one another such that a line of the sample preparation cartridge module 208 is about aligned with a line of the wells 214.
- the device 200 further comprises an input device 218, such as a touch screen display, and the like, which may be used to control the device 200 into a loading mode, which causes the cassette access door 204 and the well access door 210 to open such that the cassette 206 and the well holder 212, with the wells 214, may be manually loaded into the device 200.
- a sample preparation cartridge module 208 is loaded with a sample 238 (e.g. such as a biological sample retrieved from a human by medical personnel), and the like, via a port 220.
- the input device 218 may also be used to set given temperatures to which the sample preparation cartridge module 208 is to be heated and/or a heating cycle of the sample preparation cartridge module 208 and/or a heating/mixing cycle(e.g. setting mixing speeds of the actuator 116 of the device 200).
- a cassette carriage 224 of the device 200 is raised along a vertical carriage guide 226 to at least partially emerge from an opening that is normally covered by the cassette access door 204.
- the cassette 206 is then manually loaded into the cassette carriage 224.
- a well carriage e.g. a shuttle
- a horizontal carriage guide e.g. a planar surface
- the well holder 212 is then manually loaded into a complementary shaped depression and/or holder 231 in the well carriage 228.
- vertical and horizontal are used herein with regards to a position of the device 200 in a normal use mode, such terms are meant for ease of description only and/or to indicate relative positions of components of the device 200 (e.g. the guides 226, 230 may be about perpendicular to each other as one is vertical and the other horizontal, but may be in any suitable orientation).
- the cassette carriage 224 moves the cassette 206 into different positions in the device 200 (e.g. closing the door 204), for example along the vertical carriage guide 226, to process the sample 238 before dispensing the sample 238 from the sample preparation cartridge module 208 into a well 214.
- the device 200 is further understood to include a motor and/or a servomotor, and the like, to move the cassette carriage 224 into different positions along the vertical carriage guide 226.
- the horizontal carriage guide 230 moves inside the device 200 (e.g. closing the door 210) and the well carriage 228 is moved into a position to receive the sample 238 from the sample preparation cartridge module 208 into a corresponding well 214.
- the well carriage 228 is moved into respective positions to receive respective samples 238 dispensed from respective sample preparation cartridge modules 208 into corresponding wells 214.
- the well carriage 228 may be positioned at an angle relative to the cassette carriage 224 and/or the cassette 206 such that different sample preparation cartridge modules 208 align with different wells 214 at different positions of the well carriage 228.
- the device 200 is further understood to include motors and/or a servomotors, and the like, to move the horizontal carriage guide 230 into and out of the device 200, and to linearly move the well carriage 228 along the horizontal carriage guide 230.
- the device 200 may further include respective components for opening and closing the doors 204, 210.
- the sample preparation cartridge module 208 may be divided into a first region 232 and a second region 234, divided by a barrier 236.
- a sample 238 is received into the sample preparation cartridge module 208 via the port 220, and may resides at a bottom of the first region 232, at the barrier 236.
- the sample preparation cartridge module 208 may further comprise an agitator 240 in the first region 232 which may be actuated via a mixer actuator 242 and an actuator 116, and the like of the device 200 as described below.
- the mixer actuator 242 may include a servomotor and/or servomotors, and the like, to move/rotate the actuator 116 to mix the sample 238 via the agitator 240, while the sample 238 is heated, as described below.
- the cassette 206 may be moved, along the vertical carriage guide 226, via the cassette carriage 224, into a heating position for heating by one or both of the two heaters 102 attached to respective mechanical devices 106.
- the heaters 102 and the mechanical devices 106 are in rest positions (e.g. similar to the rest position 110).
- the device 200 is understood to include respective temperature sensors 104 at the heaters 102 and/or the mechanical devices 106 as in Figure 1A and Figure 1 B.
- the device 100 may incorporate two heaters 102, two sensors 104 and two mechanical devices 106, the heaters 102 and the mechanical devices 106 positioned to engage the sample preparation cartridge module 208 from opposite directions for example when the cassette 206 is loaded into the cassette carriage 224, and the cassette carriage 224 is in a heating position.
- the sample 238 in the sample preparation cartridge module 208 is positioned along the vertical carriage guide 226 such that the sample preparation cartridge module 208 is at a sample engaging position 108 of the heaters 102.
- the heaters 102, mechanical devices 106 and temperature sensors 104 thereof are described in further detail with respect to Figure 3, Figure 4A, Figure 4B, Figure 4C, and Figure 4D.
- the device 200 may include the circuit 114.
- the heaters 102 are about generally aligned with the sample 238 (e.g. perpendicularly), and the heaters 102 may be moved into respective sample engaging positions to heat the sample 238, while the agitator 240 is actuated by the actuator 116 to agitate and/or mix the sample 238 while it is being heated, for example to promote lysis in cells of the sample 238.
- the actuator 116 itself is understood to be further moved by the mixer actuator 242 into a position to agitate and/or mix the sample 238, while it is being heated, and actuated by the mixer actuator 242 which may comprise any suitable combination of motors for moving and turning the actuator 116.
- the first region 232 may include magnetizing microparticles (including, but not limited to, paramagnetic microparticles) having surfaces to which biological components of interest, expelled by cells of the sample 238 due to lysis, bond; hence, in some examples, the actuator 116 may comprise a magnetic agitating device which agitates the sample 238 during lysis by applying a changing magnetic field to the first region 232 to move the magnetizing microparticles; In such examples, the agitator 240 may be omitted from the sample preparation cartridge module 208.
- magnetizing microparticles including, but not limited to, paramagnetic microparticles
- the agitator 240 is generally configured to mate with the actuator 116; for example, as depicted, the agitator 240 may be attached to a pressure source 250, such as a plunger, and the like, an outer surface of which may be used to both mate with the actuator 116, to actuate the agitator 240, and move the sample 238 to the second region 234, for example by applying pressure to the pressure source 250 via the actuator 116 to break the barrier 236.
- a pressure source 250 such as a plunger, and the like, an outer surface of which may be used to both mate with the actuator 116, to actuate the agitator 240, and move the sample 238 to the second region 234, for example by applying pressure to the pressure source 250 via the actuator 116 to break the barrier 236.
- the second region 234 may further include a wash buffer which may be mixed biological components of interest bonded to the magnetizing microparticles (e.g. when plunged into the second region 234), by actuation of a suitable reservoir 252 of a plurality of reservoirs 252 that perform different functions for the sample preparation cartridge module 208; such reservoirs 252 may be alternatively referred to as blisters and/or pouches, and the like.
- one reservoir 252 may hold the wash buffer, another reservoir 252 may hold chemicals to stabilize the biological components of interest, another reservoir 252 may hold a grease barrier, and yet another reservoir 252 may be for dispensing the processed sample 238, including the biological components of interest bonded to the magnetizing microparticles, into a well 214, for example via a needle and/or tip 254 of the sample preparation cartridge module 208.
- the cassette 206 may hold a plurality of sample preparation cartridge modules 208 and hence the device 200 may include various devices for actuating a plurality of corresponding reservoirs 252 (e.g. concurrently) on a plurality of sample preparation cartridge modules 208 and devices for actuating individual reservoirs 252 (e.g. independent of each other) on the sample preparation cartridge modules 208.
- the device 200 may include a multiple reservoir actuator 256 including a plurality of reservoir tips 258 (though only one is depicted) which may be used to actuate a plurality of corresponding reservoirs 252 (e.g.
- the device 200 may include a plurality of single reservoir actuators 260 (though only one is depicted) including respective reservoir tips 262 (though, again, only one is depicted), for independently actuating respective reservoirs 252 at the plurality of sample preparation cartridge modules 208 to independently dispense samples 238 into respective wells 214 via respective tips 262.
- the device 200 may comprise one single reservoir actuator 260 including one reservoir tip 262 that is movable within the device 200 between sample preparation cartridge modules 208.
- cassette carriage 224 may be moved into various suitable positions along the vertical carriage guide 226 relative to other components of the device 200, to effect actuation of the pressure source 250 and/or actuation of respective reservoirs 252 by the reservoir actuators 256, 260.
- the device 200 and/or the sample preparation cartridge module 208 may include other suitable components.
- the sample preparation cartridge module 208 may include the magnetizing microparticles in the first region 232 which have surfaces treated to bond to biological components of interest releases from the sample 238 when heated due to lysis.
- the second region 234 may include a wash buffer density gradient, when the wash buffer is introduced into the second region 234; in particular, the second region 234 may comprise a fluid density gradient isolates and/or purifies the biological components of interest bonded to the magnetizing microparticles.
- the device 200 may include a magnet 264, which may be actuated via a magnetic actuator 266 to move the magnet 264 adjacent the sample preparation cartridge module 208 as the sample preparation cartridge module 208 is moved along the vertical carriage guide 226, for example to attract the magnetizing microparticles in the sample 238 to move the sample 238, including the biological components of interest bonded to the magnetizing microparticles, through the wash buffer density gradient in the second region 234 to isolate and/or purify the biological components of interest bonded to the magnetizing microparticles, and/or move the processed sample 238, with biological components of interest bonded to the magnetizing microparticles, to the tip 254.
- a magnet 264 which may be actuated via a magnetic actuator 266 to move the magnet 264 adjacent the sample preparation cartridge module 208 as the sample preparation cartridge module 208 is moved along the vertical carriage guide 226, for example to attract the magnetizing microparticles in the sample 238 to move the sample 238, including the biological components of interest bonded to the magnetizing microparticles, through the wash buffer density
- the device 200 further includes a cooler and/or air-intake port 268 and/or tube which may include a fan, and the like (not depicted) for drawing air into the device 200 via a filter 270, and an exhaust port 272 (which may also include a fan) for expelling air drawn into the device 200 via the cooler port 268 via a respective filter 274.
- the ports 268, 272 may provide passive and/or active cooling at the device 200 to cool the sample 238 when heated.
- the ports 268, 272 may be located in any respective suitable positions at the device 200.
- a fans of the ports 268, 272 may be controlled to assist with cooling sample preparation cartridge modules 208 as described herein.
- the cassette carriage 224 may be moved into a dispensing position relative to the wells 214 to dispense samples 238 into the wells 214. Thereafter, the wells 214 holding the samples 238 (e.g. with the biological component of interest bonded to the magnetizing microparticles, and the like) may be moved out of the device 200 via the well access door 210 and transferred, for example, to a PCR assay device.
- the wells 214 holding the samples 238 e.g. with the biological component of interest bonded to the magnetizing microparticles, and the like
- Figure 3 is substantially similar to Figure 2B with like components having like numbers.
- the cassette 206 has been loaded into the cassette carriage 224, and lowered to a heating position relative to the heaters 102, and the cassette access door 204 has been closed.
- the heaters 102 have been moved, via the mechanical devices 106, to engage at least a portion of the first region 232 of the sample preparation cartridge module 208 to heat the sample 238.
- the heaters 102 and mechanical devices 106 are in sample engaging positions (e.g. similar to the sample engaging positions 108).
- the mixer actuator 242 has been moved to cause the actuator 116 to engage the agitator 240 and the mixer actuator 242 is being controlled (e.g. via processor and/or a circuit of the device 200) to turn the actuator 116, which turns the agitator 240 to mix the sample 238.
- Figure 3 also depicts the well holder 212 and wells 214 loaded into the well carriage 228, with the horizontal carriage guide 230 moved into the device 200, with the well access door 210 closed.
- Figure 4A, Figure 4B, Figure 4C, and Figure 4D respectively show the heaters 102-1 , 102-2 and the mechanical devices 106-1 , 106-2 of the device 200 in various rest positions 110 (e.g. as in Figure 2A) and sample engaging positions 108 (e.g. as in Figure 3).
- Figure 4A, Figure 4B, Figure 4C, and Figure 4D further depict a sample preparation cartridge module 208 at the sample engaging positions 108.
- the actuator 116 is being controlled to mix the sample 238 via engaging the agitator 240.
- the heater 102-2 and the sensor 104-2 are depicted in dashed lines to show a position thereof at the mechanical devices 106-2, as the heater 102-2 and the sensor 104-2 are understood to be seen “through” the mechanical device 106-2 due to the angle of perspective.
- the sensor 104-1 is depicted in dashed lines to show a position of the sensor 104-1 relative to the sample preparation cartridge module 208, as the sensor 104-1 is understood to be seen “through” the sample preparation cartridge module 208.
- Figure 4A depicts the heaters 102 at respective rest positions 110 and Figure 4B depicts the heaters 102 engaging the sample preparation cartridge module 208 from opposite sides at respective sample engaging positions 108.
- the heaters 102 engage a portion of the first region 232 of the sample preparation cartridge module 208 to heat the sample 238.
- Figure 4A, Figure 4B, Figure 4C, and Figure 4D show that one, both, or none of the heaters 102 may be controlled to heat the sample preparation cartridge module 208.
- Figure 4A may represent the position of the heaters 102 before and after heating and/or during cooling
- Figure 4B, Figure 4C, and Figure 4D may represent different combinations of positions of the heaters 102 during heating.
- Control of the heaters 102 and the mechanical devices 106 are further understood to occur via the circuit 114 which may include a processor and have access to a memory storing various parameters as will be next described.
- Figure 5 is a block diagram of control components of the device 200 that includes the circuit 114, and which may include a processor 500 which is incorporated into the circuit 114 or, as depicted, separate from the circuit 114. While other components of the device 200 are not depicted, they are nonetheless understood to be present.
- the device 200 further depicts a computer-readable medium and/or memory 502.
- the memory 502 includes instructions that, when implemented by the processor 500 and/or the circuit 114, causes the processor 500 and/or the circuit 114 to implement dual mechanical heating control at the device 200.
- the memory 502 may be a computer-readable medium such as a volatile computer- readable medium (e.g., volatile RAM, a processor cache, a processor register, etc.), a non-volatile computer-readable medium (e.g., a magnetic storage device, an optical storage device, a paper storage device, flash memory, readonly memory, non-volatile RAM, etc.), and/or the like.
- the processor 500 may be a general-purpose processor or special purpose logic, such as a microprocessor (e.g., a central processing unit, a graphics processing unit, etc.), a digital signal processor, a microcontroller, an ASIC, an FPGA, a PAL, a PLA, a PLD, etc.
- the memory 502 or the processor 500 may be distributed among a plurality of computer-readable media or a plurality of processors with the circuit 114 integrated accordingly.
- the memory 502 includes instructions 504 which may be provided in the form of a module and/or software modules (e.g., as used herein, a “module” and/or “software module” is a set of instructions that when executed or interpreted by a processor or stored at a processor-readable medium realizes a component or performs a method). Hence, for example, the instructions 504 may alternatively be replaced with an instruction module.
- a module and/or software module is a set of instructions that when executed or interpreted by a processor or stored at a processor-readable medium realizes a component or performs a method.
- the instructions 504 may alternatively be replaced with an instruction module.
- the instructions 504 when implemented by the processor 500 and/or the circuit 114, cause the processor 500 and/or the circuit 114 to control the mechanical devices 106 to move the heaters 102 based on feedback from the sensors 104, as well to control the heaters 102 to be on or off, and/or a power level thereof, as well as control the actuator 116.
- the memory 502 further stores a heating/mixing cycle 506 which may include, but is not limited to: given temperatures periods to which the sample preparation cartridge module 208 is to be heated; associated time periods to which the sample preparation cartridge module 208 is to be heated to the given temperatures; cooling time periods, for example lengths of time that the sample preparation cartridge module 208 is be cooled between being heated to given temperatures; associated mixing speeds of the actuator 116 and the like.
- fans of the ports 268, 272 may be controlled to increase or decrease speeds thereof to assist with such heating and/or cooling.
- the heating/mixing cycle 506 may be programmed at the device 200 via the input device 218, and/or at a factory.
- the memory 502 further optionally stores temperature conditions and/or interlock conditions 508 for controlling the position of the heaters 102, as described herein.
- the temperature conditions and/or interlock conditions 508 may comprise threshold temperatures at which the heaters 102 are to be moved to respective rest positions 110 and the like.
- the memory 502 may further store instructions for implementing other functionality of the device 200 including, but not limited to, movement of the carriage 224, the horizontal carriage guide 230, the well carriage 228, the mixer actuator 242, the reservoir actuators 256, 260, the magnetic actuator 266 etc.
- method 600 may be performed with the device 200 (e.g. via the circuit 114 and/or processor 500 implementing the instructions 504).
- the method 600 may be one way in which the device 200 may be configured.
- the following discussion of method 600 may lead to a further understanding of the device 200, and its various components.
- method 600 may not be performed in the exact sequence as shown, and various blocks may be performed in parallel rather than in sequence, or in a different sequence altogether.
- the method 600 may alternatively be performed with the device 100 and/or the circuit 114 thereof.
- sample preparation device 200 has been loaded with the sample preparation cartridge module 208, containing the sample 238, which has been moved to the heating position as in Figure 3.
- the device 200 controls the actuator 116 to mix the sample 238 in the sample preparation cartridge module 208 at different speeds.
- the device 200 controls one or both of the two movable heaters 102 to engage the sample preparation cartridge module 208 from opposite directions depending on a temperature of the two movable heaters 102, as measured by a temperature sensor 104 or temperature sensors 104, or a speed of the actuator 116.
- the device 200 may implement the heating/mixing cycle 506 which may include, but is not limited to, heating the sample 238 to different temperatures while being mixed at different respective speeds of the actuator 116.
- the method 600 may include the device 200: controlling the actuator 116 to a first speed; controlling both of the two movable heaters 102 to engage the sample preparation cartridge module 208 while the actuator 116 is at the first speed (e.g. as in Figure 4B); and in response to the temperature of the two movable heaters 102 reaching a given temperature: controlling the actuator 116 to a second speed; and controlling both of the two movable heaters 102 to disengage the sample preparation cartridge module 208 (e.g. as in Figure 4A) while the actuator 116 is at the second speed.
- the sample 238 is mixed at the first speed while heated to the given temperature using both heaters 102; the device 200 may control the two movable heaters 102 to maintain the given temperature for a given period of time and, thereafter, disengage the two movable heaters 102 from the sample preparation cartridge module 208 to cool the sample preparation cartridge module 208, while controlling the actuator 116 to the second speed.
- fans of the ports 268, 272 may be controlled by the device 200 to increase or decrease speeds thereof to assist with such heating and/or cooling.
- such an example may be implemented via the heating/mixing cycle 506.
- the method 600 may include the device 200: controlling the actuator 116 to a first speed; controlling one of the two movable heaters 102 to engage the sample preparation cartridge module 208 while the actuator 116 is at the first speed (e.g. as depicted in Figure 4C or Figure 4D); and in response to the temperature reaching a given temperature using one heater 102: controlling the actuator 116 to a second speed; and controlling the one of the two movable heaters 102 that has engaged the sample preparation cartridge module 208 to disengage (e.g. as in Figure 4A) the sample preparation cartridge module 208 while the actuator 116 is at the second speed.
- the device 200 may control the actuator 116 to the second speed in response to the temperature reaching a given temperature for a given time period and/or for a given elapsed time period; in particular, before controlling the actuator 116 to the second speed, the sample preparation cartridge module 208 may be held at the given temperature for the given time period.
- the sample 238 is mixed at the first speed while heated to the given temperature; the device 200 may control the one of the movable heaters 102 that has engaged the sample preparation cartridge module 208 to maintain the given temperature for a given period of time and, thereafter, disengage the movable heater 102 from the sample preparation cartridge module 208 to cool the sample preparation cartridge module 208, while controlling the actuator 116 to the second speed.
- the actuator 116 may be implemented via the heating/mixing cycle 506.
- the method 600 may include the device 200: controlling both (e.g. as in Figure 4B) of the two movable heaters 102 to engage the sample preparation cartridge module 208 while the actuator 116 is at a first speed; controlling both (e.g. as in Figure 4A) of the two movable heaters 102 to disengage the sample preparation cartridge module while the actuator 116 is at a second speed; and controlling one of the two movable heaters 102 (e.g. as in Figure 4C or Figure 4D) to engage the sample preparation cartridge module 208 while the actuator 116 is at a third speed.
- the device 200 controlling both (e.g. as in Figure 4B) of the two movable heaters 102 to engage the sample preparation cartridge module 208 while the actuator 116 is at a first speed; controlling both (e.g. as in Figure 4A) of the two movable heaters 102 to disengage the sample preparation cartridge module while the actuator 116 is at a second speed; and controlling one of the two movable heaters 102 (e.g
- the sample 238 may be mixed at the first speed, while heated using both heaters 102; the device 200 may control the actuator 116 to maintain the first speed for a first given period of time and, thereafter, disengage one of the two movable heaters 102 from the sample preparation cartridge module 208 to cool the sample preparation cartridge module 208, while controlling the actuator 116 to the second speed; the device 200 may control the actuator 116 to maintain the second speed for a second given period of time and, thereafter, disengage the engaged movable heater 102 from the sample preparation cartridge module 208 to cool the sample preparation cartridge module 208, while controlling the actuator 116 to a third speed.
- the method 600 may include the device 200: controlling both of the two movable heaters 102 to engage the sample preparation cartridge module 208 until the temperature reaches a first given temperature (e.g. which may be maintained for a first given time period); controlling both of the two movable heaters 102 to disengage the sample preparation cartridge module 208 until the temperature reaches a second given temperature (e.g. which may be maintained for a second given time period); and controlling one of the two movable heaters 102 to engage the sample preparation cartridge module until the temperature reaches a third given temperature(e.g. which may be maintained for a third given time period).
- a first given temperature e.g. which may be maintained for a first given time period
- controlling one of the two movable heaters 102 to engage the sample preparation cartridge module until the temperature reaches a
- actuator 116 and the heaters 102 may be concurrently and independently controlled to implement any suitable heating/mixing cycle, for example as defined by the heating/mixing cycle 506 stored at the memory 502.
- a sample preparation cartridge module 208 may be adapted to assist with heating. Attention is next directed to Figure 7 which depicts an example sample preparation cartridge module 208 in cross-section, and without the pressure source 250, the agitator 240 and the various reservoirs 252 which may nonetheless be present.
- Figure 7 depicts the first region 232 and the second region 234 separated by the barrier 236 as well as the tip 254.
- the first region 232 and the second region 234 may be understood to be fluidly connected, at least when the barrier 236 is broken.
- the first region 232 may comprising a heating region.
- the second region 234 may store a heat sensitive chemical, for example at least when particular reservoirs 252 are actuated, such as the aforementioned wash buffer, chemicals to stabilize the sample 238 and/or the biological component of interest, and/or the grease barrier.
- the sample preparation cartridge module 208 is depicted in crosssection, respective inner walls 702-1 , 702-2 (e.g. inner walls 702 and/or an inner wall 702) and external walls 704-1 , 704-2 (e.g. external walls 704 and/or an external wall 704) of the first region 232 and the second region 234 are shown.
- the first region 232 comprises: an internal wall 702-1 formed from a first material 706 having a first thermal conductivity, and an external wall 704-2 that includes a second material 708 having a second thermal conductivity higher than the first thermal conductivity. Furthermore, the second material 708 is absent from the internal wall 702-1 .
- the second region 234 comprises: a respective internal wall 702-2 and a respective external wall 704-2 both formed from the first material 706.
- the second material 708 is absent from the second region 234.
- the second material 708 having a second thermal conductivity higher than the first thermal conductivity of the first material 706, is located at the first region 232 which is engaged by the heaters 102, the second material 708 promotes heat conduction from the heaters 102 to the sample 238 contained in the first region 232, through the walls 702-1 , 704-1 of the first region 232.
- the external wall 704-1 of the first region 232 is understood to be shaped to mate with a heater 102, as described in the present specification.
- the two heaters 102 are understood to be further shaped to engage a heating region (e.g.
- the first region 232) of the sample preparation cartridge module 208 having an internal wall 702-1 formed from the first material 706 having a first thermal conductivity, and an external wall 704-1 that includes a second material 708 having a second thermal conductivity higher than the first thermal conductivity, the second material 708 absent from the internal wall 704-1 , wherein adjacent regions of the sample preparation cartridge module 208, including, but not limited to the second region 234, are absent the second material 708 to contain heat from the heaters 102 at the heating region as will next be described.
- the second material 708 may be selected regardless of whether or not it may react with the sample 238 as the first material 706 at the inner wall 702-2 shields the sample 238 from the second material 708.
- the second material 708 is located at the external wall 704- 1 of the first region 232, and as the walls 702-2, 704-2 of the second region 234 comprise the first material 706 having a lower thermal conductivity than the second material 708, the walls 702-2, 704-2 of the second region 234 act to thermally insulate the second region 236 from heat in the first region 232.
- the first material 706 may be selected to be chemically inert to the sample 238 and any chemicals in the second region 234.
- the first material 706 may comprises a cyclic olefin copolymer (CoC) material from which the walls 702, 704 of the sample preparation cartridge module 208 are formed, other than the portion of the external wall 704-1 of the first region 232 that includes the second material 708.
- the first material 706 may comprise any suitable material.
- the second material 708 comprises metal, aluminum, copper, carbon, carbon fiber, carbon powder, graphite, a metallic powder, a metal oxide powder, or aluminum oxide.
- the second material 708 may comprise any suitable material, though a type of the second material 708 may depend, however, on how the second material 708 is incorporated at the external wall 704-1 .
- the external wall 704-1 of the first region 232 may comprise an insert of the second material 708, provided, for example, in the form of a compression fit sleeve or a slug of the second material pressed, or molded, into the external wall 704-1 of the first material 706 of the first region 232, and the like, which wraps at least partially around the first region 232.
- the second material 708 may comprise a metal, aluminum or copper, and the like.
- the insert may be provided at the external wall 704-1 of the first region 232 during an insertion molding process that otherwise forms the sample preparation cartridge module 208 and/or the insert may be provided at the external wall 704-1 of the first region 232 after formation of the remainder of the walls 702, 704 of the sample preparation cartridge module 208.
- the external wall 704-1 of the first region 232 may comprise a mixture of the first material 706 and the second material 708, for example at the location of the second material 708 indicated in Figure 7, provided during an insertion molding process that forms the sample preparation cartridge module 208.
- the first material 706 and the second material 708 may be provided as mixture and in a form compatible with insertion molding.
- the second material 708 may comprise carbon, carbon fiber, carbon powder, graphite, a metallic powder, a metal oxide powder, or aluminum oxide, and the like.
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Abstract
An example device comprises: two heaters shaped to engage a sample preparation cartridge module from opposite directions; two mechanical devices to respectively move the heaters between respective sample engaging positions and respective rest positions; two temperature sensors to respectively measure temperature of the two heaters; an actuator to mix a sample in the sample preparation cartridge module at different speeds; and a circuit communicatively coupled to the two heaters, the two mechanical devices, and the actuator. The circuit is to control the actuator to mix a sample in the sample preparation cartridge module at the different speeds; and control one or both of the two mechanical devices to move one or both of the two heaters to the respective sample engaging positions or the respective rest positions depending on temperatures measured by the two temperature sensors or a speed of the actuator.
Description
Dual mechanical heating control
BACKGROUND
[0001] Sample heating in devices that effect biological or chemical processes in sample preparation cartridge modules can be crucial, for example in sample preparation devices.
BRIEF DESCRIPTION OF THE DRAWINGS
[0002] Reference will now be made, by way of example only, to the accompanying drawings in which:
[0003] Figure 1 A and Figure 1 B are block diagrams of an example device with dual mechanical heating control, with heaters thereof in rest positions and sample engaging positions respectively.
[0004] Figure 2A is a perspective view of an example sample preparation device that incorporates the device of Figure 1 .
[0005] Figure 2B is a block diagram of the device of Figure 2A.
[0006] Figure 3 is a block diagram of the device of Figure 2A showing a cassette and sample preparation cartridge module in a heating position.
[0007] Figure 4A, Figure 4B, Figure 4C, and Figure 4D show heaters of the device of Figure 2A in rest positions and sample engaging positions respectively, as well as a sample preparation cartridge module at the sample engaging positions.
[0008] Figure 5 is a block diagram showing control components of the device of Figure 2A, such as a processor, to implement dual mechanical heating control.
[0009] Figure 6 is a flow diagram of an example method for dual mechanical heating control.
[0010] Figure 7 depicts a cross-section of an example sample preparation cartridge module.
DETAILED DESCRIPTION
[0011] In biological assays, a biological component can be intermixed with other components in a biological sample that can interfere with subsequent analysis. As used herein, the term “biological component” can refer to materials of various types, including proteins, cells, cell nuclei, nucleic acids, bacteria, viruses, or the like, that can be present in a biological sample. A “biological sample” can refer to a fluid or a dried or lyophilized material obtained for analysis from a living or deceased organism. Isolating the biological component from other components of the biological sample can permit subsequent analysis without interference and can increase an accuracy of the subsequent analysis. In addition, isolating a biological component from other components in a biological sample can permit analysis of the biological component that would not be possible if the biological component remained in the biological sample. In this context, “Isolation” can also be referred to as “purification”, whereby biological component may be separated from the rest of the biological sample after introduction to a sample preparation cartridge module interchangeably referred to hereafter as a sample container, a sample dispensing container, a cartridge module, and the like. It will be understood that the isolated biological component may be output in association with (e.g., bound to) particulate substrate and a reagent solution, or the like. The isolation or purification refers to the separation of the biological component from other components of the biological sample with which it was originally introduced in the cartridge module, but it does not mean that the biological component is completely isolated when it is dispensed. For example, isolation refers to the fact that the biological component is sufficiently separated or “purified” from other components of the original biological sample to facilitate further processing such as detection and/or amplification.
[0012] Many isolation techniques can include repeatedly dispersing and reaggregating samples. The repeated dispersing and re-aggregating can result in a loss of a quantity of the biological component. Furthermore, isolating a biological component with some of these techniques can be complex, time consuming, and labor intensive and can result in less than maximum yields of the isolated biological component. Such Isolation techniques are done using specific devices.
[0013] Obtaining precise biological sample preparation devices can be challenging due to many moving parts present in the devices, for example to move a carriage holding a cartridge of sample dispensing containers relative to sample receiving wells. The cartridge may hold a plurality of the sample dispensing containers or sample preparation devices or sample preparation cartridge modules which contain different respective biological samples.
[0014] During the isolation process, The sample dispensing containers or sample preparation devices or sample preparation cartridge modules may heat the samples to perform for example, lysis on cells in the biological samples to release biological component of interest, coming from the biological sample, may be a nucleic acid (such as DNA or RNA). Resulting sample fluid may be drawn through a fluid density gradient in the sample dispensing containers and dispensed into sample receiving wells, which may be transferred to further analytical assay such as, for example, a Polymerase Chain Reaction (PCR).
[0015] However, as initial quantities of the biological component of interest present in the biological sample, may be small, precise dispensing of the component of interest from the sample dispensing containers into the sample receiving wells should occur so as to not lose any content and/or to prevent cross-contamination between samples. As such a precise determination of a position of a shuttle and/or well carriage, that holds the sample receiving wells, relative to the carriage is important, and vice versa.
[0016] In some examples, the device of the present disclosure is a device that can be used to prepare sample to be used in a process of preparing samples for a PCR (polymerase chain reaction) assay. PCR assays are processes that can rapidly copy millions to billions of copies of a very small DNA or RNA sample. PCR can be used for many different application, included sequencing genes, diagnosing viruses, identifying cancers, and others. In the PCR process, a small sample of DNA or RNA is combined with reactants that can form copies of the DNA or RNA.
[0017] As described herein, the biological sample comprises a biological component. In some examples, the biological component of interest, coming
from the biological sample, may be a nucleic acid (such as DNA or RNA). A particulate substrate can be configured to be associated with the biological component, to isolate the biological component from the biological sample. In one example, the particulate substrate comprises paramagnetic beads and/or any magnetizing particle and/or magnetizing microparticles. In one example, the biological component comprises nucleic acids such as DNA and/or RNA that may be extracted from the biological sample by lysing, bound to magnetic particulate substrate, and separated from the lysate and dragged towards an output by an externally generated (para)magnetic force. Lysate may refer to the fluid containing the material resulting from the lysis of a biological sample. Such lysis may release the biological component that is contained therein. Lysing itself may include mixing and/or heating the biological sample, chemically lysing the biological sample, and/or a combination of the foregoing.
[0018] Hence, as will now be apparent, sample heating in such devices, that process biological samples, as described above, in sample containers and/or sample preparation cartridge modules, can be crucial.
[0019] As such, provided herein is a device that that includes two heaters attached to respective mechanical devices that move the heaters between respective sample engaging positions, to heat a sample preparation cartridge module at the sample engaging positions, and respective rest positions and/or a cooling positions, at which the heaters do not heat the sample preparation cartridge module. The two heaters are generally positioned and shaped to engage a sample preparation cartridge module from opposite directions. The device includes two temperature sensors to respectively measure temperature of the two heaters. The device further includes an actuator to mix a sample in the sample preparation cartridge module at different speeds. A circuit generally controls the actuator to mix a sample in the sample preparation cartridge module at the different speeds while concurrently controlling one or both of the two mechanical devices to move one or both of the two heaters to the respective sample engaging positions or the respective rest positions depending on temperatures measured by the two temperature sensors or a speed of the actuator. The device may be incorporated into the aforementioned sample
preparation device, and the like, which receives sample preparation cartridge module containing biological samples, for example human cells to be tested for presence of a biological component of interest; hence, with two heaters that may singly, or doubly, engage a sample preparation cartridge module, the sample preparation device may achieve flexibility in performing heating on a sample in the sample preparation cartridge module for lysis, and the like.
[0020] In particular, the circuit may control one or both of two heaters to engage the sample preparation cartridge module from opposite directions depending on a temperature of the two heaters, as measured by a temperature sensor, and/or depending on a speed of the actuator, for example to better control lysis in the samples.
[0021] In some examples, a sample preparation cartridge module provided herein may be formed from a first material that has a first thermal conductivity. Internal walls of the sample preparation cartridge module are understood to be formed from the first material, which may be chemically inert to samples, and other materials, that are contained within the sample preparation cartridge module by the internal wall. A heating region of the sample preparation cartridge module, for example within which a sample resides for lysis to be performed thereon, may have an external wall that includes a second material having a second thermal conductivity higher than the first thermal conductivity. The second material may be otherwise absent from internal walls of the sample preparation cartridge module as well regions of the sample preparation cartridge module other than the heating region. The second material may hence promote thermal conductivity in the heating region to better heat a sample contained therein to perform lysis; absence of the second material at the internal walls may allow the second material to include materials reactive to samples and/or other chemicals contained within the sample preparation cartridge module. Furthermore, absence of the second material outside the heating region may better contain heat in the heating region and/or prevent heat from being conducted to other regions of the sample preparation cartridge module, as the other regions are formed from the first material that has the first thermal conductivity lower than the second thermal conductivity of the second material.
[0022] A first aspect of the specification provides a device comprising: two heaters shaped to engage a sample preparation cartridge module from opposite directions; two mechanical devices to respectively move the heaters between respective sample engaging positions and respective rest positions; two temperature sensors to respectively measure temperature of the two heaters; an actuator to mix a sample in the sample preparation cartridge module at different speeds; and a circuit communicatively coupled to the two heaters, the two mechanical devices, and the actuator, to circuit to: control the actuator to mix a sample in the sample preparation cartridge module at the different speeds; and control one or both of the two mechanical devices to move one or both of the two heaters to the respective sample engaging positions or the respective rest positions depending on temperatures measured by the two temperature sensors or a speed of the actuator.
[0023] At the device of the first aspect, the circuit may be further to, in response to the temperatures meeting a temperature condition, control one or both of the heaters to stop heating.
[0024] At the device of the first aspect, the two heaters may be further shaped to engage a heating region of the sample preparation cartridge module having an internal wall formed from a first material having a first thermal conductivity, and an external wall that includes a second material having a second thermal conductivity higher than the first thermal conductivity, the second material absent from the internal wall, wherein adjacent regions of the sample preparation cartridge module are absent the second material to contain heat from the heaters at the heating region.
[0025] At the device of the first aspect, the two mechanical devices may comprise respective robotic arms, the two heaters located at respective end effectors of the robotic arms.
[0026] At the device of the first aspect, the circuit may be further to independently control respective power to the two heaters.
[0027] A second aspect of the specification provides a method comprising: controlling, at a sample preparation device into which a sample preparation
cartridge module has been loaded, an actuator to mix a sample in the sample preparation cartridge module at different speeds; and controlling, at the sample preparation device, one or both of two movable heaters to engage the sample preparation cartridge module from opposite directions depending on a temperature of the two movable heaters, as measured by a temperature sensor, or a speed of the actuator.
[0028] The method of the second aspect may further comprise: controlling the actuator to a first speed; controlling both of the two movable heaters to engage the sample preparation cartridge module while the actuator is at the first speed; and in response to the temperature of the two movable heaters reaching a given temperature: controlling the actuator to a second speed; and controlling both of the two movable heaters to disengage the sample preparation cartridge module while the actuator is at the second speed.
[0029] The method of the second aspect may further comprise: controlling the actuator to a first speed; controlling one of the two movable heaters to engage the sample preparation cartridge module while the actuator is at the first speed; and in response to the temperature reaching a given temperature: controlling the actuator to a second speed; and controlling the one of the two movable heaters that has engaged the sample preparation cartridge module to disengage the sample preparation cartridge module while the actuator is at the second speed.
[0030] The method of the second aspect may further comprise: controlling both of the two movable heaters to engage the sample preparation cartridge module while the actuator is at a first speed; controlling both of the two movable heaters to disengage the sample preparation cartridge module while the actuator is at a second speed; and controlling one of the two movable heaters to engage the sample preparation cartridge module while the actuator is at a third speed.
[0031] The method of the second aspect may further comprise: controlling both of the two movable heaters to engage the sample preparation cartridge module until the temperature reaches a first given temperature; controlling both of the two movable heaters to disengage the sample preparation cartridge module
until the temperature reaches a second given temperature; and controlling one of the two movable heaters to engage the sample preparation cartridge module until the temperature reaches a third given temperature.
[0032] A third aspect of the present specification provides a sample preparation cartridge module comprising: a first region comprising: an internal wall formed from a first material having a first thermal conductivity, and an external wall that includes a second material having a second thermal conductivity higher than the first thermal conductivity, the second material absent from the internal wall; and a second region comprising: a respective internal wall and a respective external wall both formed from the first material, the second material absent from the second region, the first region and the second region being fluidly connected, the first region comprising a heating region and the second region storing a heat sensitive chemical.
[0033] At the sample preparation cartridge module of the third aspect, the external wall of the first region may comprise an insert of the second material, or a mixture of the first material and the second material.
[0034] At the sample preparation cartridge module of the third aspect, the first material may comprise a cyclic olefin copolymer (CoC) material.
[0035] At the sample preparation cartridge module of the third aspect, the second material may comprise metal, aluminum, copper, carbon, carbon fiber, carbon powder, graphite, a metallic powder, a metal oxide powder, or aluminum oxide.
[0036] At the sample preparation cartridge module of the third aspect, the external wall of the first region may be shaped to mate with a heater.
[0037] Figure 1 A and Figure 1 B show respective block diagrams of an example device 100 with dual mechanical heating control with heaters thereof in respective rest positions and sample positions. While described in more detail below, it is understood that components of the device 100 may be components of a larger device used for medical testing of samples including, but not limited to, sample preparation. In particular, the device 100 may be used in a larger
sample preparation device to process samples in sample preparation cartridge modules, and the like. Such a sample preparation device is described below with respect to Figure 2A and Figure 2B.
[0038] The device 100 generally comprises two heaters 102-1 , 102-2, represented in Figure 1A and Figure 1 B as resistors, and two temperature sensors 104-1 , 104-2 represented in Figure 1A and Figure 1 B as thermistors. The heaters 102-1 , 102-2 are interchangeably referred to hereafter, collectively, as the heaters 102 and, generically, as a heater 102. This convention will be used throughout the present specification; for example, the temperature sensors 104-1 , 104-2 may be referred as the sensors 104 and/or as a sensor 104.
[0039] The device 100 further comprises two mechanical devices 106-1 , 106-2 (e.g. mechanical devices 106 and/or a mechanical device 106) to move respective heaters 102 between respective sample engaging positions 108, as depicted in Figure 1 B, and respective rest positions 110, as depicted in Figure 1A.
[0040] In Figure 1A and Figure 1 B, the heater 102-1 and the sensor 104-2 are depicted in dashed lines to show a position thereof at the mechanical device 106-2, as the heater 102-1 and the sensor 104-2 are understood to be seen “through” the mechanical device 106-2 due to the angle of perspective.
[0041] As depicted, the heaters 102 (and/or the mechanical devices 106) are shaped, and positioned relative to one another, to engage a sample preparation cartridge module from opposite directions.
[0042] For example, the heaters 102 and/or the mechanical devices 106 may include respective chassis, and the like, that are shaped complementary to a sample preparation cartridge module located at the sample engaging positions 108 (e.g. see Figure 4B). In a particular example, as depicted, chassis of the heaters 102 and/or the mechanical devices 106 are concave to engage a cylindrically shaped sample preparation cartridge module at the sample engaging positions 108. However, the heaters 102 and/or the mechanical devices 106 may be any suitable shape to heat a sample preparation cartridge module (e.g. which may also be of any suitable shape).
[0043] In general, the device 100 further comprises a circuit 114 and an actuator 116. The actuator 116 is generally to mix a sample in a sample preparation cartridge module between the two heaters 102 at different speeds and may be actuated by a mixer actuator, not depicted (however see Figure 2B). Such mixing is indicated by an arrow 118 in Figure 1 B showing the actuator 116 being rotated back and forth (and the like). Interaction of the actuator 116 with a sample preparation cartridge module is described in more detail below.
[0044] The circuit 114 is communicatively coupled to the heaters 102, the temperature sensors 104, the mechanical devices 106 and the actuator 116. While electrical connections from the circuit 114 to the various other components are not explicitly depicted, such electrical connections and/or communicative couplings are represented by double ended arrows between the circuit 114 the mechanical devices 106 and the actuator 116 which may represent wiring, and the like, of the circuit 114 to the various other components.
[0045] The circuit 114 is generally to control the actuator 116 to mix a sample (e.g. a liquid sample) in a sample preparation cartridge module, engaged by the heaters 102, at the different speeds; and control one or both of the two mechanical devices 106 to move one or both of the two heaters 102 to the respective sample engaging positions 108 or the respective rest positions 110, depending on temperatures measured by the two temperature sensors 104 or a speed of the actuator 116.
[0046] Put another way, the circuit 114 generally controls the mechanical devices 106 to move one or both of the heaters 102 to engage a sample preparation cartridge module while also controlling the speed of the actuator 116; the speed of the actuator 116 may be a given speed at which a sample in the sample preparation cartridge module is to be heated to a particular given temperature, during a given heating/mixing cycle, which may be achieved by controlling the mechanical devices 106 to move one or both of the heaters 102 to engage the sample preparation cartridge module.
[0047] While not depicted, it is understood that the device 100 further comprises a power source, which powers the components of the device 100, including, but
not limited to, the heaters 102, such that the heaters 102 are powered to perform heating. Such a power source may include, but is not limited to, a connection to a mains power supply and/or batteries, and the like,
[0048] The heaters 102 may comprise any suitable heating devices including, but not limited to, the depicted resistors incorporated into chassis, and the like, which may be shaped to engage a sample preparation cartridge module. It is generally understood that the heaters 102 are positioned at the device 100 to be adjacent and/or against (e.g. via a wall of chassis of the heaters 102 and/or the mechanical devices 106) a sample preparation cartridge module at the sample engaging positions 108. It is understood that the chassis of the heaters 102 and/or the mechanical devices 106 may comprise thermally conducting material, such as any suitable combination of metal and/or a thermally conducting plastic, and the like, to conduct heat from the heaters 102 to a sample preparation cartridge module.
[0049] In some examples, a portion of the material of the chassis of the heaters 102 and/or the mechanical devices 106 that reside against a sample preparation cartridge module may be (e.g. optionally) at least partially elastic, and the like, to at least partially mold around a sample preparation cartridge module at the sample engaging positions 108, to assist with thermal conduction from the heaters 102 to the sample preparation cartridge module.
[0050] In general, the heaters 102 may be controlled to respective on-states or off-states (e.g. on or off) by the circuit 114. However, the heaters 102 may alternatively be controlled to different heating levels in the on-states, to heat a sample preparation cartridge module at the sample engaging positions 108 to different temperatures, as monitored by the temperature sensors 104. Alternatively, the heaters 102 may be controlled between an on-state and off- state to heat a sample preparation cartridge module at the sample engaging positions 108 to a given temperature and/or different temperatures using pulse width modulation (PWM) control of the heaters 102 (e.g. to control, by the circuit 114, respective relative time periods that the heaters 102 are respectively on or off).
[0051] However, the heaters 102 may also heat a sample preparation cartridge module at the sample engaging positions 108 to different temperatures by the circuit 114 controlling the mechanical devices 106 to move the heaters 102 to different positions, relative to the sample engaging positions 108. For example, the closer the heaters 102 are to the sample engaging positions 108, the more heating of a sample preparation cartridge module at the sample engaging positions 108 may occur. Alternatively, such control of the mechanical devices 106 may also occur according to PWM control (e.g. to control, by the circuit 114, respective relative time periods that the heaters 102 are at respective sample engaging positions 108 or the respective rest positions 110).
[0052] Regardless, it is understood that the heaters 102 are independently movable relative to the sample engaging positions 108 and hence may alternatively be referred to as movable heaters 102.
[0053] It is further understood that the heaters 102 may be controlled to a given temperature (e.g. by the circuit 114) in a feedback loop, based on feedback from the sensors 104.
[0054] The temperatures sensors 104 may comprise any suitable temperature sensing device and/or circuit including, but not limited to, the depicted thermistors incorporated into respective chassis, and the like, at which the respective heaters 102 are also incorporated. It is generally understood that the sensors 104 is positioned at the device 100 to be adjacent and/or against (e.g. via a wall of a chassis of the heaters 102 and/or the mechanical devices 106) a sample preparation cartridge module at the sample engaging positions 108. As such, the sensors 104 generally measure temperature changes due to the heaters 102 being turned on or off by the circuit 114 (and/or otherwise being generally controlled by the circuit 114).
[0055] As depicted the temperature sensors 104 are depicted as being at a respective chassis, and the like, at which a respective heater 102 is also incorporated, and hence, as depicted, the temperature sensors 104 also move with the heaters 102. Put another way, the temperature sensors 104 may be located at respective heaters 102.
[0056] However, in other examples the temperature sensors 104 may be at respective fixed positions, for example at respective sample engaging positions 108, and include components for engaging a sample preparation cartridge module at the sample engaging positions 108. For example, the temperature sensors 104 may be incorporated into respective spring loaded arms which causes the sensors 104 to reside against a sample preparation cartridge module at the sample engaging positions 108.
[0057] A mechanical device 106 may comprise any suitable mechanical device which moves a respective heater 102 between a respective sample engaging position 108 and a respective rest position 110, including, but not limited to, a robotic arm, an arm attached to a servomotor, and the like. An optical encoder, and the like, at the robotic arm and/or the servomotor may be used to control a respective mechanical device 106 between a respective sample engaging position 108 and a respective rest position 110.
[0058] Regardless, the heaters 102 may be understood to be located at respective end effector positions of respective mechanical devices 106 (e.g. ends of the mechanical devices 106 that interact with an environment around the mechanical devices 106 including, but not limited to, a sample preparation cartridge module at the sample engaging positions 108). Put another way, the two mechanical devices 106 may comprise respective robotic arms or respective arms and servomotors, and the two heaters 102 may be located at respective end effector positions of the mechanical devices 106.
[0059] While the mechanical devices 106 are depicted as controlling the heaters 102 to the sample engaging positions 108 and the rest positions 110, it is understood that the mechanical devices 106 may alternatively to be controlled (e.g. by the circuit 114) to move the heaters 102 to any suitable respective position between the respective sample engaging positions 108 and the respective rest positions 110, for example to control respective positions of the heaters 102 relative to a sample preparation cartridge module at the sample engaging positions 108 to control a heating cycle at the sample preparation cartridge module.
[0060] Such a heating cycle may include, but is not limited to, respective times that the sample preparation cartridge module are at respective given temperatures as measured by the sensors 104, ramp times to reach such temperatures, cooling times, and the like. Furthermore, such a heating cycle may be part of a heating/mixing cycle in which the heaters 102 are controlled to heat while the actuator 116 is controlled to mix.
[0061] Furthermore, in some examples, the mechanical devices 106 may be controlled (e.g. by the circuit 114) to adjust the position of the heaters 102 by adjusting respective mechanical pressure or respective mechanical force at the sample engaging positions 108. For example, respective robotic arms and/or a respective servomotors, and the like, of the mechanical devices 106 may be controlled (e.g. by the circuit 114) to position respective heaters 102 against a sample preparation cartridge module at respective sample engaging positions 108. and apply respective mechanical pressure and/or respective mechanical force to the sample preparation cartridge module at the respective sample engaging positions 108, for example to change and/or control thermal contact and/or thermal conduction between the heaters 102 and a sample preparation cartridge module. In some of these examples, the mechanical devices 106 may be spring loaded to apply respective mechanical pressure or respective mechanical force at the sample engaging positions 108.
[0062] Put another way, the circuit 114 may be further to control the mechanical devices 106 to adjust the respective positions of the heaters 102, to control a heating cycle, by adjusting mechanical pressure or mechanical force at the sample engaging positions 108.
[0063] For example, while not depicted, the device 100 and/or the mechanical devices 106 may include respective pressure sensors and/or force sensors to measure pressure and/or force applied by the mechanical devices 106, and such pressure sensors and/or force sensors may be used to control respective pressure and/or force applied by the mechanical devices 106 in a feedback loop and/or feedback loops with the circuit 114. Alternatively, the respective pressure and/or force applied by the mechanical devices 106 may be controlled via
optical encoder positions of servomotors of the mechanical devices 106 and/or in any other suitable manner.
[0064] A heating cycle, and/or a heating/mixing cycle, may also be controlled by controlling respective time periods that the heaters 102 are at the sample engaging positions 108. For example, the circuit 114 may be further to control the mechanical devices 106 to adjust the position of the heaters 102, to control a heating cycle, by controlling respective time periods that the heaters 102 are at the sample engaging positions 108. In particular, the circuit 114 may be further to control a heating cycle by controlling power to the heaters 102, such that a heater 102 or heaters 102 are turned on for a given time period, to a power level or different power levels, and then turned off. Put another way, the circuit 114 may be further to independently control respective power to the two heaters 102.
[0065] The circuit 114 may comprise any suitable combination of components to control the heaters 102, and the mechanical devices 106 based on temperature measured by the sensors 104 or a speed of the actuator 116. For example, the circuit 114 may comprise connections to the heaters 102, a power source to power the heaters 102, switches and/or other components to turn the heaters 102 on or off and/or to adjust a current and/or power to the heaters 102 to control the heaters 102 to different heating levels. In general, the circuit 114 is to control the heaters 102 to a given temperature and/or given temperatures, for example to control a heating cycle of a sample preparation cartridge module at the sample engaging positions 108.
[0066] In some examples, the circuit 114 may comprise a proportional-integral- derivative controller (PID) controller and/or PID controllers to control the heaters 102 to a given temperature and/or given temperatures, for example to control a heating cycle and/or heating cycles and/or heating/mixing cycles of a sample preparation cartridge module at the sample engaging positions 108 based on feedback from the sensors 104.
[0067] The circuit 114 may further comprise connections to the mechanical devices 106, and/or a servomotor thereof, to control the mechanical devices 106
to move the heaters 102 relative to the sample engaging positions 108. In a simple example, the circuit 114 may independently control the mechanical devices 106 to move the heaters 102 to respective sample engaging positions 108 or respective rest positions 110. For example, the circuit 114 may control one or both of the mechanical devices 106 to move one or both of the heaters 102 to the sample engaging positions 108 to heat a sample preparation cartridge module, and the circuit 114 may control one or both of the mechanical devices 106 to move one or both of heaters 102 to the rest positions 110 to cool the sample preparation cartridge module
[0068] In some of these examples, the circuit 114 may control the heaters 102 to be on when the mechanical devices 106 are controlled to move the heaters 102 to the sample engaging positions 108 for example to heat the sample preparation cartridge module to a given temperature and/or for a given period of time to effect lysis and the like at the sample preparation cartridge module. The circuit 114 may then control the heaters 102 to be off when the mechanical devices 106 are controlled to move the heaters 102 to the rest position 110 for example after the given period of time.
[0069] Furthermore, the circuit 114 may coordinate mixing speeds of the actuator 116 with given temperatures to which the heaters 102 are heated, as described in more detail below with respect to Figure 6.
[0070] Furthermore, in some examples, the circuit 114 may be further to, in response to temperatures measured by the sensors 104 meeting a temperature condition, control one or both of the heaters 102 to stop heating and/or control the mechanical devices 106 to move the heaters 102 to the rest positions 110. For example, such temperature conditions may alternatively be referred to as interlock conditions as, in response to the temperatures meeting a temperature condition, such as a threshold temperature and/or an overshoot temperature, the controlling of the mechanical devices 106 to move the heaters 102 from the sample engaging positions 108 to the rest positions 110 and/or turning off the heaters 102, may act as an interlock to prevent damage to a sample preparation cartridge module at the sample engaging positions 108 and/or sample
contained in the sample preparation cartridge module. The temperature condition may be that the temperatures monitored by the temperature sensors 104 have reached or exceeded a threshold temperature above which it is undesirable to heat a sample, as at some temperature, above the threshold temperature, biological components of interest in the sample may be damaged and/or the device 100 may be damaged and/or other components of a larger sample preparation device into which the device 100 is incorporated may be damaged. In some examples, such a threshold temperature may be referred to as an overheat temperature. Alternatively, the temperature condition may be associated with preventing device damage. For example, the temperature condition may be that the temperatures monitored by the temperature sensors 104 has reached or exceeded a threshold temperature above which the device 100 may be damaged and/or other components of a larger sample preparation device into which the device 100 is incorporated may be damaged. Such rises in temperature, to the threshold temperature, may be due to a fault in the heaters 102 and/or the circuit 114 and/or the sample preparation cartridge module any other suitable condition.
[0071] The circuit 114 may include any suitable combination of switches, electrical circuits, and the like which implement functionality as described herein. In some examples, the circuit 114 may further include a general-purpose processor and/or controller or special purpose logic, such as a microprocessor and/or microcontroller (e.g. a central processing unit (CPU) and/or a graphics processing unit (GPU) an integrated circuit or other circuitry), an application specific integrated circuit (ASIC), a Field Programmable Gate Array (FPGA), a programmable array logic (PAL), a programmable logic array (PLA), a programmable logic device (PLD), and the like. Hence, functionality of the circuit 114 may be implemented as a combination of hardware (e.g. a CPU, a GPU, etc.) and software (e.g., programming such as machine- or processorexecutable instructions, commands, or code such as firmware, a device driver, programming, object code, etc. as stored on hardware). Alternatively, the circuit 114 may be implemented as a hardware element with no software elements (e.g. such as an ASIC, an FPGA, a PAL, a PLA, a PLD etc.).
[0072] While not depicted, given temperatures, heating/mixing cycles, positions of the mechanical devices 106 (and optionally temperature conditions), and the like, may be stored at a memory of the device 100 (e.g. see Figure 5), along with instructions for controlling the circuit 114 and/or a processor thereof (e.g. when the circuit is implemented as combination of hardware and software). Such a memory may include, but is not limited to, any suitable combination of a volatile computer-readable medium (e.g., volatile RAM, a processor cache, a processor register, etc.), a non-volatile computer-readable medium (e.g., a magnetic storage device, an optical storage device (e.g. a Digital Versatile Disc (DVD), a paper storage device, flash memory, read-only memory, non-volatile RAM, etc.), and/or the like.
[0073] Attention is next directed to Figure 2A and Figure 2B which respectively depict a perspective view and a block diagram of an example sample preparation device 200 that incorporates aspects of the device 100 of Figure 1 . As depicted, the sample preparation device 200 (interchangeably referred to hereafter as the device 200) includes a chassis 202 that includes a cassette access door 204 for loading a cassette 206 that includes a sample preparation cartridge module 208 and/or sample preparation cartridge modules 208 therein, the sample preparation cartridge module 208 holding a sample for testing as described hereafter. While the sample preparation cartridge modules 208 are depicted herein as being in an elongate shape, the sample preparation cartridge modules 208 may be any suitable shape. The chassis 202 further includes a well access door 210 for loading a well holder 212 containing a well 214 and/or wells for receiving processed samples dispensed from the sample preparation cartridge module 208 after processing by the device 200. While only one sample preparation cartridge module 208 is depicted, and eight wells 214, it is understood that the cassette 206 may hold a same number of sample preparation cartridge modules 108 as there are wells 214 at the well holder 212. For example, as depicted, there may be eight sample preparation cartridge modules 208 and eight wells 214. Furthermore, while the cassette 206 is depicted in an end view showing only one sample preparation cartridge module 208, and the well holder 212 is shown in a front view showing eight wells 214,
the components of the device 200 may cause the cassette 206 and the well holder 212 to be loaded into the device 200 in any suitable relative orientation including, but not limited to, about parallel to one another such that a line of the sample preparation cartridge module 208 is about aligned with a line of the wells 214.
[0074] As depicted, the device 200 further comprises an input device 218, such as a touch screen display, and the like, which may be used to control the device 200 into a loading mode, which causes the cassette access door 204 and the well access door 210 to open such that the cassette 206 and the well holder 212, with the wells 214, may be manually loaded into the device 200. Hence, it is understood that a sample preparation cartridge module 208 is loaded with a sample 238 (e.g. such as a biological sample retrieved from a human by medical personnel), and the like, via a port 220. The input device 218 may also be used to set given temperatures to which the sample preparation cartridge module 208 is to be heated and/or a heating cycle of the sample preparation cartridge module 208 and/or a heating/mixing cycle(e.g. setting mixing speeds of the actuator 116 of the device 200).
[0075] In the loading mode, a cassette carriage 224 of the device 200 is raised along a vertical carriage guide 226 to at least partially emerge from an opening that is normally covered by the cassette access door 204. The cassette 206 is then manually loaded into the cassette carriage 224.
[0076] Similarly, in the loading mode, a well carriage (e.g. a shuttle) 228, which moves linearly on a horizontal carriage guide (e.g. a planar surface) 230, is moved out of an opening that is normally covered by the well access door 210, for example by moving and/or rotating and end of horizontal carriage guide 230 at which the well carriage 228 is located in the loading mode, out of the opening. The well holder 212 is then manually loaded into a complementary shaped depression and/or holder 231 in the well carriage 228. While the terms vertical and horizontal are used herein with regards to a position of the device 200 in a normal use mode, such terms are meant for ease of description only and/or to indicate relative positions of components of the device 200 (e.g. the
guides 226, 230 may be about perpendicular to each other as one is vertical and the other horizontal, but may be in any suitable orientation).
[0077] Once loaded, the cassette carriage 224 moves the cassette 206 into different positions in the device 200 (e.g. closing the door 204), for example along the vertical carriage guide 226, to process the sample 238 before dispensing the sample 238 from the sample preparation cartridge module 208 into a well 214. As such, while not depicted, the device 200 is further understood to include a motor and/or a servomotor, and the like, to move the cassette carriage 224 into different positions along the vertical carriage guide 226.
[0078] Similarly, once loaded, the horizontal carriage guide 230 moves inside the device 200 (e.g. closing the door 210) and the well carriage 228 is moved into a position to receive the sample 238 from the sample preparation cartridge module 208 into a corresponding well 214. When there a plurality of sample preparation cartridge modules 208 holding respective samples 238, once the samples 238 are processed, the well carriage 228 is moved into respective positions to receive respective samples 238 dispensed from respective sample preparation cartridge modules 208 into corresponding wells 214. As such, the well carriage 228 may be positioned at an angle relative to the cassette carriage 224 and/or the cassette 206 such that different sample preparation cartridge modules 208 align with different wells 214 at different positions of the well carriage 228.
[0079] As such, while not depicted, the device 200 is further understood to include motors and/or a servomotors, and the like, to move the horizontal carriage guide 230 into and out of the device 200, and to linearly move the well carriage 228 along the horizontal carriage guide 230.
[0080] While not depicted, the device 200 may further include respective components for opening and closing the doors 204, 210.
[0081] To effect processes of the device 200, the sample preparation cartridge module 208 may be divided into a first region 232 and a second region 234, divided by a barrier 236. A sample 238 is received into the sample preparation
cartridge module 208 via the port 220, and may resides at a bottom of the first region 232, at the barrier 236. The sample preparation cartridge module 208 may further comprise an agitator 240 in the first region 232 which may be actuated via a mixer actuator 242 and an actuator 116, and the like of the device 200 as described below. In particular, the mixer actuator 242 may include a servomotor and/or servomotors, and the like, to move/rotate the actuator 116 to mix the sample 238 via the agitator 240, while the sample 238 is heated, as described below.
[0082] For example, the cassette 206 may be moved, along the vertical carriage guide 226, via the cassette carriage 224, into a heating position for heating by one or both of the two heaters 102 attached to respective mechanical devices 106. As depicted in Figure 2B, it is understood that the heaters 102 and the mechanical devices 106 are in rest positions (e.g. similar to the rest position 110).
[0083] While not depicted in Figure 2B, the device 200 is understood to include respective temperature sensors 104 at the heaters 102 and/or the mechanical devices 106 as in Figure 1A and Figure 1 B. Put another way, the device 100 may incorporate two heaters 102, two sensors 104 and two mechanical devices 106, the heaters 102 and the mechanical devices 106 positioned to engage the sample preparation cartridge module 208 from opposite directions for example when the cassette 206 is loaded into the cassette carriage 224, and the cassette carriage 224 is in a heating position. In the heating position, shown in Figure 3, described below, the sample 238 in the sample preparation cartridge module 208 is positioned along the vertical carriage guide 226 such that the sample preparation cartridge module 208 is at a sample engaging position 108 of the heaters 102.
[0084] The heaters 102, mechanical devices 106 and temperature sensors 104 thereof are described in further detail with respect to Figure 3, Figure 4A, Figure 4B, Figure 4C, and Figure 4D. Furthermore, while not depicted in Figure 2B, the device 200 may include the circuit 114.
[0085] When the cassette 206 is moved to a heating position of the device 200,
the heaters 102 are about generally aligned with the sample 238 (e.g. perpendicularly), and the heaters 102 may be moved into respective sample engaging positions to heat the sample 238, while the agitator 240 is actuated by the actuator 116 to agitate and/or mix the sample 238 while it is being heated, for example to promote lysis in cells of the sample 238. As such, the actuator 116 itself is understood to be further moved by the mixer actuator 242 into a position to agitate and/or mix the sample 238, while it is being heated, and actuated by the mixer actuator 242 which may comprise any suitable combination of motors for moving and turning the actuator 116. Alternatively, as will be explained in further detail below, the first region 232 may include magnetizing microparticles (including, but not limited to, paramagnetic microparticles) having surfaces to which biological components of interest, expelled by cells of the sample 238 due to lysis, bond; hence, in some examples, the actuator 116 may comprise a magnetic agitating device which agitates the sample 238 during lysis by applying a changing magnetic field to the first region 232 to move the magnetizing microparticles; In such examples, the agitator 240 may be omitted from the sample preparation cartridge module 208.
[0086] However, as depicted, it is understood that the agitator 240 is generally configured to mate with the actuator 116; for example, as depicted, the agitator 240 may be attached to a pressure source 250, such as a plunger, and the like, an outer surface of which may be used to both mate with the actuator 116, to actuate the agitator 240, and move the sample 238 to the second region 234, for example by applying pressure to the pressure source 250 via the actuator 116 to break the barrier 236.
[0087] Once lysis is performed on the sample 238, biological components of interest may be released from the sample 238 and bond to the magnetizing microparticles. While not depicted, the second region 234 may further include a wash buffer which may be mixed biological components of interest bonded to the magnetizing microparticles (e.g. when plunged into the second region 234), by actuation of a suitable reservoir 252 of a plurality of reservoirs 252 that perform different functions for the sample preparation cartridge module 208;
such reservoirs 252 may be alternatively referred to as blisters and/or pouches, and the like. For example, one reservoir 252 may hold the wash buffer, another reservoir 252 may hold chemicals to stabilize the biological components of interest, another reservoir 252 may hold a grease barrier, and yet another reservoir 252 may be for dispensing the processed sample 238, including the biological components of interest bonded to the magnetizing microparticles, into a well 214, for example via a needle and/or tip 254 of the sample preparation cartridge module 208.
[0088] As mentioned above, the cassette 206 may hold a plurality of sample preparation cartridge modules 208 and hence the device 200 may include various devices for actuating a plurality of corresponding reservoirs 252 (e.g. concurrently) on a plurality of sample preparation cartridge modules 208 and devices for actuating individual reservoirs 252 (e.g. independent of each other) on the sample preparation cartridge modules 208. For example, as depicted, the device 200 may include a multiple reservoir actuator 256 including a plurality of reservoir tips 258 (though only one is depicted) which may be used to actuate a plurality of corresponding reservoirs 252 (e.g. concurrently) on a plurality of sample preparation cartridge modules 208, for example to concurrently introduce the wash buffer, or the stabilizing chemicals or the grease barrier into the second regions 234 of the plurality of sample preparation cartridge modules 208. However, the device 200 may include a plurality of single reservoir actuators 260 (though only one is depicted) including respective reservoir tips 262 (though, again, only one is depicted), for independently actuating respective reservoirs 252 at the plurality of sample preparation cartridge modules 208 to independently dispense samples 238 into respective wells 214 via respective tips 262. In other examples, the device 200 may comprise one single reservoir actuator 260 including one reservoir tip 262 that is movable within the device 200 between sample preparation cartridge modules 208.
[0089] It is understood that the cassette carriage 224 may be moved into various suitable positions along the vertical carriage guide 226 relative to other components of the device 200, to effect actuation of the pressure source 250 and/or actuation of respective reservoirs 252 by the reservoir actuators 256,
260.
[0090] The device 200 and/or the sample preparation cartridge module 208 may include other suitable components. For example, as mentioned above, the sample preparation cartridge module 208 may include the magnetizing microparticles in the first region 232 which have surfaces treated to bond to biological components of interest releases from the sample 238 when heated due to lysis. Furthermore, the second region 234 may include a wash buffer density gradient, when the wash buffer is introduced into the second region 234; in particular, the second region 234 may comprise a fluid density gradient isolates and/or purifies the biological components of interest bonded to the magnetizing microparticles. As depicted, the device 200 may include a magnet 264, which may be actuated via a magnetic actuator 266 to move the magnet 264 adjacent the sample preparation cartridge module 208 as the sample preparation cartridge module 208 is moved along the vertical carriage guide 226, for example to attract the magnetizing microparticles in the sample 238 to move the sample 238, including the biological components of interest bonded to the magnetizing microparticles, through the wash buffer density gradient in the second region 234 to isolate and/or purify the biological components of interest bonded to the magnetizing microparticles, and/or move the processed sample 238, with biological components of interest bonded to the magnetizing microparticles, to the tip 254.
[0091] As depicted, the device 200 further includes a cooler and/or air-intake port 268 and/or tube which may include a fan, and the like (not depicted) for drawing air into the device 200 via a filter 270, and an exhaust port 272 (which may also include a fan) for expelling air drawn into the device 200 via the cooler port 268 via a respective filter 274. In particular, the ports 268, 272 may provide passive and/or active cooling at the device 200 to cool the sample 238 when heated. Furthermore, the ports 268, 272 may be located in any respective suitable positions at the device 200. Furthermore, when such cooling is active, a fans of the ports 268, 272 may be controlled to assist with cooling sample preparation cartridge modules 208 as described herein.
[0092] Finally, once the samples 238 are processed as described, the cassette carriage 224 may be moved into a dispensing position relative to the wells 214 to dispense samples 238 into the wells 214. Thereafter, the wells 214 holding the samples 238 (e.g. with the biological component of interest bonded to the magnetizing microparticles, and the like) may be moved out of the device 200 via the well access door 210 and transferred, for example, to a PCR assay device.
[0093] For clarity, attention is briefly directed to Figure 3 which is substantially similar to Figure 2B with like components having like numbers. However, in Figure 3, the cassette 206 has been loaded into the cassette carriage 224, and lowered to a heating position relative to the heaters 102, and the cassette access door 204 has been closed. Furthermore, the heaters 102 have been moved, via the mechanical devices 106, to engage at least a portion of the first region 232 of the sample preparation cartridge module 208 to heat the sample 238. As such, in Figure 3, it is understood that the heaters 102 and mechanical devices 106 are in sample engaging positions (e.g. similar to the sample engaging positions 108).
[0094] Furthermore, the mixer actuator 242 has been moved to cause the actuator 116 to engage the agitator 240 and the mixer actuator 242 is being controlled (e.g. via processor and/or a circuit of the device 200) to turn the actuator 116, which turns the agitator 240 to mix the sample 238.
[0095] For completeness, Figure 3 also depicts the well holder 212 and wells 214 loaded into the well carriage 228, with the horizontal carriage guide 230 moved into the device 200, with the well access door 210 closed.
[0096] Attention is next directed to Figure 4A, Figure 4B, Figure 4C, and Figure 4D which respectively show the heaters 102-1 , 102-2 and the mechanical devices 106-1 , 106-2 of the device 200 in various rest positions 110 (e.g. as in Figure 2A) and sample engaging positions 108 (e.g. as in Figure 3). Figure 4A, Figure 4B, Figure 4C, and Figure 4D further depict a sample preparation cartridge module 208 at the sample engaging positions 108. In Figure 4A, Figure 4B, Figure 4C, and Figure 4D it is further understood that the actuator
116 is being controlled to mix the sample 238 via engaging the agitator 240.
[0097] Hence, it is understood in Figure 4A, Figure 4B, Figure 4C, and Figure 4D that the cassette carriage 224 (not depicted) has been moved to a heating position in the device 200 such that the first region 232 of the sample preparation cartridge module 208, containing the sample 238, has been moved between the heaters 102 while in the rest positions 110 and then one or both of the mechanical devices 106 have been controlled, for example by the circuit 114, to move one or both the heaters 102 to the sample engaging positions 108 to engage the sample preparation cartridge module 208 and heat the sample 238.
[0098] In Figure 4A, Figure 4B, Figure 4C, and Figure 4D, the heater 102-2 and the sensor 104-2 are depicted in dashed lines to show a position thereof at the mechanical devices 106-2, as the heater 102-2 and the sensor 104-2 are understood to be seen “through” the mechanical device 106-2 due to the angle of perspective. Similarly, in Figure 4B and Figure 4D, the sensor 104-1 is depicted in dashed lines to show a position of the sensor 104-1 relative to the sample preparation cartridge module 208, as the sensor 104-1 is understood to be seen “through” the sample preparation cartridge module 208.
[0099] In particular, Figure 4A depicts the heaters 102 at respective rest positions 110 and Figure 4B depicts the heaters 102 engaging the sample preparation cartridge module 208 from opposite sides at respective sample engaging positions 108. In particular, in Figure 4B, the heaters 102 engage a portion of the first region 232 of the sample preparation cartridge module 208 to heat the sample 238.
[00100] In contrast, in Figure 4C, the mechanical device 106-1 has been controlled to move the heater 102-1 to a respective rest position 110-1 , and the mechanical device 106-2 has been controlled to move the heater 102-2 to a respective sample engaging position 108-2.
[00101] In yet further contrast, in Figure 4D, the mechanical device 106-1 has been controlled to move the heater 102-1 to a respective sample engaging position 108-1 , and the mechanical device 106-2 has been controlled to move
the heater 102-2 to a respective rest position 110-2.
[00102] Hence, Figure 4A, Figure 4B, Figure 4C, and Figure 4D show that one, both, or none of the heaters 102 may be controlled to heat the sample preparation cartridge module 208.
[00103] In particular, Figure 4A may represent the position of the heaters 102 before and after heating and/or during cooling, while Figure 4B, Figure 4C, and Figure 4D may represent different combinations of positions of the heaters 102 during heating.
[00104] Control of the heaters 102 and the mechanical devices 106 are further understood to occur via the circuit 114 which may include a processor and have access to a memory storing various parameters as will be next described.
[00105] Figure 5 is a block diagram of control components of the device 200 that includes the circuit 114, and which may include a processor 500 which is incorporated into the circuit 114 or, as depicted, separate from the circuit 114. While other components of the device 200 are not depicted, they are nonetheless understood to be present.
[00106] The device 200 further depicts a computer-readable medium and/or memory 502. The memory 502 includes instructions that, when implemented by the processor 500 and/or the circuit 114, causes the processor 500 and/or the circuit 114 to implement dual mechanical heating control at the device 200. The memory 502 may be a computer-readable medium such as a volatile computer- readable medium (e.g., volatile RAM, a processor cache, a processor register, etc.), a non-volatile computer-readable medium (e.g., a magnetic storage device, an optical storage device, a paper storage device, flash memory, readonly memory, non-volatile RAM, etc.), and/or the like. The processor 500 may be a general-purpose processor or special purpose logic, such as a microprocessor (e.g., a central processing unit, a graphics processing unit, etc.), a digital signal processor, a microcontroller, an ASIC, an FPGA, a PAL, a PLA, a PLD, etc. The memory 502 or the processor 500 may be distributed among a plurality of computer-readable media or a plurality of processors with the circuit 114 integrated accordingly.
[00107] The memory 502 includes instructions 504 which may be provided in the form of a module and/or software modules (e.g., as used herein, a “module” and/or “software module” is a set of instructions that when executed or interpreted by a processor or stored at a processor-readable medium realizes a component or performs a method). Hence, for example, the instructions 504 may alternatively be replaced with an instruction module.
[00108] In particular, the instructions 504, when implemented by the processor 500 and/or the circuit 114, cause the processor 500 and/or the circuit 114 to control the mechanical devices 106 to move the heaters 102 based on feedback from the sensors 104, as well to control the heaters 102 to be on or off, and/or a power level thereof, as well as control the actuator 116.
[00109] For example, as depicted, the memory 502 further stores a heating/mixing cycle 506 which may include, but is not limited to: given temperatures periods to which the sample preparation cartridge module 208 is to be heated; associated time periods to which the sample preparation cartridge module 208 is to be heated to the given temperatures; cooling time periods, for example lengths of time that the sample preparation cartridge module 208 is be cooled between being heated to given temperatures; associated mixing speeds of the actuator 116 and the like. During heating and/or cooling time periods, fans of the ports 268, 272 may be controlled to increase or decrease speeds thereof to assist with such heating and/or cooling. The heating/mixing cycle 506 may be programmed at the device 200 via the input device 218, and/or at a factory.
[00110] As depicted, the memory 502 further optionally stores temperature conditions and/or interlock conditions 508 for controlling the position of the heaters 102, as described herein. For example, the temperature conditions and/or interlock conditions 508 may comprise threshold temperatures at which the heaters 102 are to be moved to respective rest positions 110 and the like.
[00111] While not depicted, the memory 502 may further store instructions for implementing other functionality of the device 200 including, but not limited to, movement of the carriage 224, the horizontal carriage guide 230, the well carriage 228, the mixer actuator 242, the reservoir actuators 256, 260, the
magnetic actuator 266 etc.
[00112] Referring to Figure 6, a flow diagram of an example method 600 to perform dual mechanical heating control is depicted. In order to assist in the explanation of method 600, it will be assumed that method 600 may be performed with the device 200 (e.g. via the circuit 114 and/or processor 500 implementing the instructions 504). The method 600 may be one way in which the device 200 may be configured. Furthermore, the following discussion of method 600 may lead to a further understanding of the device 200, and its various components. Furthermore, it is to be emphasized, that method 600 may not be performed in the exact sequence as shown, and various blocks may be performed in parallel rather than in sequence, or in a different sequence altogether. Furthermore, it is to be emphasized that the method 600 may alternatively be performed with the device 100 and/or the circuit 114 thereof.
[00113] It is further understood in the method 600 that sample preparation device 200 has been loaded with the sample preparation cartridge module 208, containing the sample 238, which has been moved to the heating position as in Figure 3.
[00114] Beginning at a block 602, the device 200 controls the actuator 116 to mix the sample 238 in the sample preparation cartridge module 208 at different speeds.
[00115] At a block 604, the device 200 controls one or both of the two movable heaters 102 to engage the sample preparation cartridge module 208 from opposite directions depending on a temperature of the two movable heaters 102, as measured by a temperature sensor 104 or temperature sensors 104, or a speed of the actuator 116.
[00116] For example, at the block 602 and the block 604 the device 200 may implement the heating/mixing cycle 506 which may include, but is not limited to, heating the sample 238 to different temperatures while being mixed at different respective speeds of the actuator 116.
[00117] In a particular example, the method 600 may include the device 200:
controlling the actuator 116 to a first speed; controlling both of the two movable heaters 102 to engage the sample preparation cartridge module 208 while the actuator 116 is at the first speed (e.g. as in Figure 4B); and in response to the temperature of the two movable heaters 102 reaching a given temperature: controlling the actuator 116 to a second speed; and controlling both of the two movable heaters 102 to disengage the sample preparation cartridge module 208 (e.g. as in Figure 4A) while the actuator 116 is at the second speed. Hence, in this example, the sample 238 is mixed at the first speed while heated to the given temperature using both heaters 102; the device 200 may control the two movable heaters 102 to maintain the given temperature for a given period of time and, thereafter, disengage the two movable heaters 102 from the sample preparation cartridge module 208 to cool the sample preparation cartridge module 208, while controlling the actuator 116 to the second speed. During heating and/or cooling time periods, fans of the ports 268, 272 may be controlled by the device 200 to increase or decrease speeds thereof to assist with such heating and/or cooling. Furthermore such an example may be implemented via the heating/mixing cycle 506.
[00118] In another particular example, the method 600 may include the device 200: controlling the actuator 116 to a first speed; controlling one of the two movable heaters 102 to engage the sample preparation cartridge module 208 while the actuator 116 is at the first speed (e.g. as depicted in Figure 4C or Figure 4D); and in response to the temperature reaching a given temperature using one heater 102: controlling the actuator 116 to a second speed; and controlling the one of the two movable heaters 102 that has engaged the sample preparation cartridge module 208 to disengage (e.g. as in Figure 4A) the sample preparation cartridge module 208 while the actuator 116 is at the second speed. In some of these examples, the device 200 may control the actuator 116 to the second speed in response to the temperature reaching a given temperature for a given time period and/or for a given elapsed time period; in particular, before controlling the actuator 116 to the second speed, the sample preparation cartridge module 208 may be held at the given temperature for the given time period.
[00119] Hence, in this example, the sample 238 is mixed at the first speed while heated to the given temperature; the device 200 may control the one of the movable heaters 102 that has engaged the sample preparation cartridge module 208 to maintain the given temperature for a given period of time and, thereafter, disengage the movable heater 102 from the sample preparation cartridge module 208 to cool the sample preparation cartridge module 208, while controlling the actuator 116 to the second speed. Furthermore such an example may be implemented via the heating/mixing cycle 506.
[00120] In yet another particular example, the method 600 may include the device 200: controlling both (e.g. as in Figure 4B) of the two movable heaters 102 to engage the sample preparation cartridge module 208 while the actuator 116 is at a first speed; controlling both (e.g. as in Figure 4A) of the two movable heaters 102 to disengage the sample preparation cartridge module while the actuator 116 is at a second speed; and controlling one of the two movable heaters 102 (e.g. as in Figure 4C or Figure 4D) to engage the sample preparation cartridge module 208 while the actuator 116 is at a third speed. Furthermore such an example may be implemented via the heating/mixing cycle 506.
[00121] Hence, in this example, the sample 238 may be mixed at the first speed, while heated using both heaters 102; the device 200 may control the actuator 116 to maintain the first speed for a first given period of time and, thereafter, disengage one of the two movable heaters 102 from the sample preparation cartridge module 208 to cool the sample preparation cartridge module 208, while controlling the actuator 116 to the second speed; the device 200 may control the actuator 116 to maintain the second speed for a second given period of time and, thereafter, disengage the engaged movable heater 102 from the sample preparation cartridge module 208 to cool the sample preparation cartridge module 208, while controlling the actuator 116 to a third speed.
[00122] In yet another particular example, the method 600 may include the device 200: controlling both of the two movable heaters 102 to engage the
sample preparation cartridge module 208 until the temperature reaches a first given temperature (e.g. which may be maintained for a first given time period); controlling both of the two movable heaters 102 to disengage the sample preparation cartridge module 208 until the temperature reaches a second given temperature (e.g. which may be maintained for a second given time period); and controlling one of the two movable heaters 102 to engage the sample preparation cartridge module until the temperature reaches a third given temperature(e.g. which may be maintained for a third given time period). Furthermore such an example may be implemented via the heating/mixing cycle 506.
[00123] Such examples illustrate that the actuator 116 and the heaters 102 may be concurrently and independently controlled to implement any suitable heating/mixing cycle, for example as defined by the heating/mixing cycle 506 stored at the memory 502.
[00124] In some examples, a sample preparation cartridge module 208 provided herein may be adapted to assist with heating. Attention is next directed to Figure 7 which depicts an example sample preparation cartridge module 208 in cross-section, and without the pressure source 250, the agitator 240 and the various reservoirs 252 which may nonetheless be present. In particular, Figure 7 depicts the first region 232 and the second region 234 separated by the barrier 236 as well as the tip 254. The first region 232 and the second region 234 may be understood to be fluidly connected, at least when the barrier 236 is broken. As has already been described, the first region 232 may comprising a heating region. Furthermore, the second region 234 may store a heat sensitive chemical, for example at least when particular reservoirs 252 are actuated, such as the aforementioned wash buffer, chemicals to stabilize the sample 238 and/or the biological component of interest, and/or the grease barrier.
[00125] As the sample preparation cartridge module 208 is depicted in crosssection, respective inner walls 702-1 , 702-2 (e.g. inner walls 702 and/or an inner wall 702) and external walls 704-1 , 704-2 (e.g. external walls 704 and/or an external wall 704) of the first region 232 and the second region 234 are shown.
[00126] As is also depicted in Figure 7, the first region 232 comprises: an internal wall 702-1 formed from a first material 706 having a first thermal conductivity, and an external wall 704-2 that includes a second material 708 having a second thermal conductivity higher than the first thermal conductivity. Furthermore, the second material 708 is absent from the internal wall 702-1 .
[00127] As is also depicted in Figure 7, the second region 234 comprises: a respective internal wall 702-2 and a respective external wall 704-2 both formed from the first material 706. In particular, the second material 708 is absent from the second region 234.
[00128] As the second material 708, having a second thermal conductivity higher than the first thermal conductivity of the first material 706, is located at the first region 232 which is engaged by the heaters 102, the second material 708 promotes heat conduction from the heaters 102 to the sample 238 contained in the first region 232, through the walls 702-1 , 704-1 of the first region 232.
[00129] Hence, the external wall 704-1 of the first region 232 is understood to be shaped to mate with a heater 102, as described in the present specification. In particular, in these examples, the two heaters 102 are understood to be further shaped to engage a heating region (e.g. the first region 232) of the sample preparation cartridge module 208, having an internal wall 702-1 formed from the first material 706 having a first thermal conductivity, and an external wall 704-1 that includes a second material 708 having a second thermal conductivity higher than the first thermal conductivity, the second material 708 absent from the internal wall 704-1 , wherein adjacent regions of the sample preparation cartridge module 208, including, but not limited to the second region 234, are absent the second material 708 to contain heat from the heaters 102 at the heating region as will next be described.
[00130] In particular, as the second material 708 is located at the external wall 704-1 , but not the internal wall 702-1 , more flexibility is provided in selecting the second material 708 than if the walls 702-1 , 704-1 where both made of the second material 708. In particular, the second material 708 may be selected
regardless of whether or not it may react with the sample 238 as the first material 706 at the inner wall 702-2 shields the sample 238 from the second material 708.
[00131] Similarly, as the second material 708 is located at the external wall 704- 1 of the first region 232, and as the walls 702-2, 704-2 of the second region 234 comprise the first material 706 having a lower thermal conductivity than the second material 708, the walls 702-2, 704-2 of the second region 234 act to thermally insulate the second region 236 from heat in the first region 232. Furthermore, the first material 706 may be selected to be chemically inert to the sample 238 and any chemicals in the second region 234.
[00132] In some examples, the first material 706 may comprises a cyclic olefin copolymer (CoC) material from which the walls 702, 704 of the sample preparation cartridge module 208 are formed, other than the portion of the external wall 704-1 of the first region 232 that includes the second material 708. However, the first material 706 may comprise any suitable material.
[00133] In some examples, the second material 708 comprises metal, aluminum, copper, carbon, carbon fiber, carbon powder, graphite, a metallic powder, a metal oxide powder, or aluminum oxide. However, the second material 708 may comprise any suitable material, though a type of the second material 708 may depend, however, on how the second material 708 is incorporated at the external wall 704-1 .
[00134] For example, the external wall 704-1 of the first region 232 may comprise an insert of the second material 708, provided, for example, in the form of a compression fit sleeve or a slug of the second material pressed, or molded, into the external wall 704-1 of the first material 706 of the first region 232, and the like, which wraps at least partially around the first region 232. In these examples, the second material 708 may comprise a metal, aluminum or copper, and the like.
[00135] The insert may be provided at the external wall 704-1 of the first region 232 during an insertion molding process that otherwise forms the sample preparation cartridge module 208 and/or the insert may be provided at the
external wall 704-1 of the first region 232 after formation of the remainder of the walls 702, 704 of the sample preparation cartridge module 208.
[00136] Alternatively, the external wall 704-1 of the first region 232 may comprise a mixture of the first material 706 and the second material 708, for example at the location of the second material 708 indicated in Figure 7, provided during an insertion molding process that forms the sample preparation cartridge module 208. In these examples, the first material 706 and the second material 708 may be provided as mixture and in a form compatible with insertion molding. In these examples, the second material 708 may comprise carbon, carbon fiber, carbon powder, graphite, a metallic powder, a metal oxide powder, or aluminum oxide, and the like.
[00137] It should be recognized that features and aspects of the various examples provided above may be combined into further examples that also fall within the scope of the present disclosure.
Claims
1 . A device comprising: two heaters shaped to engage a sample preparation cartridge module from opposite directions; two mechanical devices to respectively move the heaters between respective sample engaging positions and respective rest positions; two temperature sensors to respectively measure temperature of the two heaters; an actuator to mix a sample in the sample preparation cartridge module at different speeds; and a circuit communicatively coupled to the two heaters, the two mechanical devices, and the actuator, to circuit to: control the actuator to mix a sample in the sample preparation cartridge module at the different speeds; and control one or both of the two mechanical devices to move one or both of the two heaters to the respective sample engaging positions or the respective rest positions depending on temperatures measured by the two temperature sensors or a speed of the actuator.
2. The device of claim 1 , wherein the circuit is further to, in response to the temperatures meeting a temperature condition, control one or both of the heaters to stop heating.
3. The device of claim 1 , wherein the two heaters are further shaped to engage a heating region of the sample preparation cartridge module having an internal wall formed from a first material having a first thermal conductivity, and an external wall that includes a second material having a second thermal conductivity higher than the first thermal conductivity, the second material absent from the internal wall, wherein adjacent regions of the sample preparation cartridge module are absent the second material to contain heat from the heaters at the heating region.
37
4. The device of claim 1 , wherein the two mechanical devices comprise respective robotic arms, the two heaters located at respective end effectors of the robotic arms.
5. The device of claim 1 , wherein the circuit is further to independently control respective power to the two heaters.
6. A method comprising: controlling, at a sample preparation device into which a sample preparation cartridge module has been loaded, an actuator to mix a sample in the sample preparation cartridge module at different speeds; and controlling, at the sample preparation device, one or both of two movable heaters to engage the sample preparation cartridge module from opposite directions depending on a temperature of the two movable heaters, as measured by a temperature sensor, or a speed of the actuator.
7. The method of claim 6, further comprising: controlling the actuator to a first speed; controlling both of the two movable heaters to engage the sample preparation cartridge module while the actuator is at the first speed; and in response to the temperature of the two movable heaters reaching a given temperature: controlling the actuator to a second speed; and controlling both of the two movable heaters to disengage the sample preparation cartridge module while the actuator is at the second speed.
8. The method of claim 6, further comprising: controlling the actuator to a first speed; controlling one of the two movable heaters to engage the sample preparation cartridge module while the actuator is at the first speed; and in response to the temperature reaching a given temperature: controlling the actuator to a second speed; and controlling the one of the two movable heaters that has engaged the sample preparation cartridge module to disengage the sample preparation cartridge module while the actuator is at the second speed.
9. The method of claim 6, further comprising: controlling both of the two movable heaters to engage the sample
preparation cartridge module while the actuator is at a first speed; controlling both of the two movable heaters to disengage the sample preparation cartridge module while the actuator is at a second speed; and controlling one of the two movable heaters to engage the sample preparation cartridge module while the actuator is at a third speed.
10. The method of claim 6, further comprising: controlling both of the two movable heaters to engage the sample preparation cartridge module until the temperature reaches a first given temperature; controlling both of the two movable heaters to disengage the sample preparation cartridge module until the temperature reaches a second given temperature; and controlling one of the two movable heaters to engage the sample preparation cartridge module until the temperature reaches a third given temperature.
11. A sample preparation cartridge module comprising: a first region comprising: an internal wall formed from a first material having a first thermal conductivity, and an external wall that includes a second material having a second thermal conductivity higher than the first thermal conductivity, the second material absent from the internal wall; and a second region comprising: a respective internal wall and a respective external wall both formed from the first material, the second material absent from the second region, the first region and the second region being fluidly connected, the first region comprising a heating region and the second region storing a heat sensitive chemical.
12. The sample preparation cartridge module of claim 1 , wherein the external wall of the first region comprises an insert of the second material, or a mixture of the first material and the second material.
13. The sample preparation cartridge module of claim 1 , wherein the first material comprises a cyclic olefin copolymer (CoC) material.
14. The sample preparation cartridge module of claim 1 , wherein the second material comprises metal, aluminum, copper, carbon, carbon fiber, carbon powder, graphite, a metallic powder, a metal oxide powder, or aluminum oxide.
15. The sample preparation cartridge module of claim 1 , wherein the external wall of the first region is shaped to mate with a heater.
Priority Applications (1)
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PCT/US2020/066601 WO2022139812A1 (en) | 2020-12-22 | 2020-12-22 | Dual mechanical heating control |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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PCT/US2020/066601 WO2022139812A1 (en) | 2020-12-22 | 2020-12-22 | Dual mechanical heating control |
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WO2022139812A1 true WO2022139812A1 (en) | 2022-06-30 |
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WO2013135878A1 (en) * | 2012-03-16 | 2013-09-19 | Stat-Diagnostica & Innovation, S.L. | A test cartridge with integrated transfer module |
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WO2014071256A1 (en) * | 2012-11-05 | 2014-05-08 | California Institute Of Technology | Instruments for biological sample preparation devices |
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EP2179025B1 (en) * | 2007-07-13 | 2016-10-05 | Handylab, Inc. | Intergrated apparatus for performing nucleic acid extraction and diagnostic testing on multiple biological samples |
WO2013135878A1 (en) * | 2012-03-16 | 2013-09-19 | Stat-Diagnostica & Innovation, S.L. | A test cartridge with integrated transfer module |
WO2014046687A1 (en) * | 2012-09-24 | 2014-03-27 | Hewlett-Packard Development Company, L.P. | Microfluidic mixing device |
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